Schrneisser,   H.C. 
Leukaemia  in 
the  fowl. 


5 


BIOLOGY 
LIBRARY 

G 


THE  JOHNS  HOPKINS  HOSPITAL  REPORTS 
MONOGRAPHS.     NEW  SERIES  No.  VIII. 


LEUKAEMIA  OF  THE  FOWL: 

SPONTANEOUS  AND 

EXPERIMENTAL 


BY 

HARRY  C.  SCHMEISSER,  M.  D. 

(From  the  Department  of  Pathology  of  The  Johns  Hopkins  University) 
Illustrated :  4  Plates 


UNiV,    OF  • 

>      >    ;       )     i  > 


BALTIMORE 

THE  JOHNS  HOPKINS  PRESS 
1915 

[Copyright,  1915,  by  The  Johns  Hopkins  Press] 


CONTENTS.  . 

PAGE 

I.  Review  of  the  Literature 1 

II.  Studies  on  the  Normal  Fowl 9 

1.  External  Appearance 9 

2.  Blood 9 

3.  Autopsy  Protocol   (gross) 11 

4.  Microscopical  Examination  13 

III.  A  Case  of  Spontaneous  Leukaemia 15 

1.  Blood 15 

2.  Autopsy  Protocol  (gross) 16 

3.  Microscopical  Examination   17 

4.  Summary 19 

5.  Conclusion 20 

IV.  Experimental  Leukaemia 20 

1.  Preparation  of  Material,  Methods  of  Injection,  etc 20 

2.  Clinical  History 21 

3.  The  Blood  22 

4.  Autopsy  Findings  (gross  and  microscopical) 24 

5.  Table:    Weights  of  Body,  Organs  and  Relation  of  Organs  to 

Body  at  Autopsy 30 

6.  Summary    ; . .; . ;.-. '...'..-I.... .'. 30 

7.  Conclusion .'•.-.'.•. .';.'..:..'... ... .'. 31 

V.  Conclusion    ,                                                                                 ,..-..       .  31 


•  •         v 

•  *»     ,     .      •  »••.»,  V*t«  I  I  ,*• 

•       M.  •     ?;»  i  » J»»  »%»  *  »»• 
•.,•:•.:.. :t   ••••%«•••»' 


LEUKAEMIA  OF  THE   FOWL:    SPONTANEOUS  AND 
EXPERIMENTAL.  *  f 

By  HARRY  C.  SCHMEISSER,  M.  D. 
(From  the  Department  of  Pathology  of  The  Johns  Hopkins  University.) 

I.  REVIEW  or  THE  LITERATURE. 

The  first  publication  was  made  by  Moore '  in  1895-1896,  in  which 
he  reported  observations  upon  an  epizootic  disease  of  fowls  which  he 
designated  "  infectious  leukaemia."  His  studies  were  based  upon  cases 
obtained  from  five  different  outbreaks,  and  upon  those  artificially 
produced  by  means  of  the  specific  organism  (Bacterium  sanguinarium) 
isolated  from  the  organs  of  these  fowls.  The  descriptions  of  the 
spontaneous  and  experimental  cases  clearly  show  that  he  was  not 
dealing  with  a  true  leukaemia  of  the  fowl,  but  rather  with  an  acute 
infectious  disease,  characterized  by  fever,  diminution  in  the  number 
of  red  blood  cells,  and  increase  in  number  of  white  blood  cells,  this 
increase  being  "  restricted  "  to  the  polymorphonuclear  leucocyte  with 
the  eosin  staining  spindles,  i.  e.,  the  phagocyte  of  the  normal  fowl's 
blood. 

Butterfield,2  in  1905,  reported  three  cases  of  aleukaemic  lymph- 
adenoid  tumors  of  the  hen.  His  studies  were  limited  to  the  livers 
of  these  animals.  They  correspond  in  every  detail,  both  grossly  and 
microscopically;  were  uniformly  and  strikingly  enlarged  (340,  420, 
270  gm.  respectively)  and  of  a  diffuse,  light,  cream,  yellow  color. 
Histologically,  the  liver  tissue  was  extensively  replaced  by  large  oval 
or  round,  sometimes  irregular,  collections  of  cells.  The  intralobular 
capillaries  were  filled  with  the  usual  nucleated  red  blood  cells.  Most 
of  the  nodules  of  tumor  cells  were  thought  to  be  in  connection 
with  the  portal  spaces.  The  cells  resembled  in  general  the  "large 

*  Submitted  for  publication,  October,  1914. 

f  Dissertation  submitted  to  the  Board  of  University  Studies  of  The  Johns 
Hopkins  University,  in  conformity  with  the  requirements  for  the  Degree  of 
Doctor  of  Philosophy,  1914. 


415283 


'2*  Harry  C.  Schmeisser. 

lymphocyte "  of  the  hen's  blood.  *  Allowing  for  flattening  due  to 
pressure,  these  cells  were  round  or  oval,  with  round  or  oval  nuclei, 
mostly  eccentric.  The  nuclear  chromatin  appeared  granular  or 
reticular.  The  nucleus  was  not  infrequently  pale  and  vesicular  with 
one  or  more  bright  chromatin  bodies.  The  cytoplasm  was  present  as 
a  narrow  rim,  non-granular,  and  basophilic.  Mitoses  were  common. 
Between  these  cells  was  seen  a  delicate  reticulum.  In  association  with 
these  tumor  masses  were  quite  large  collections  of  eosinophilic  cells, 
the  majority  showing  a  single,  pale,  round  or  oval,  eccentric  nucleus 
and  a  relatively  abundant  cytoplasm,  filled  with  large,  round,  elongated, 
or  spindle-shaped  oxyphilic  structures.  They  varied  greatly  in  size 
and  shape.  The  lymphocytes  and  eosinophiles  were  occasionally 
seen  in  the  capillaries,  but  there  was  "  certainly  no  definite  increase 
within  the  blood-vessels/'  From  the  character  of  the  cells,  their  rela- 
tion to  the  portal  spaces  and  absence  of  the  lymphsemia,  the  condi- 
tion was  regarded  by  Butterfield  as  a  proliferation  of  periportal 
lymphadenoid  tissue,  and  thought  by  him  to  merit  the  designation 
"  aleukaemic  lymphadenoma." 

Mohler  had  under  observation  five  similar  cases  showing  lymphaemia 
and  the  same  lymphadenoid  condition.  Mohler's  description  of  two 
of  his  cases,  as  presented  by  Butterfield,  is  as  follows:  The  process 
showed  a  tendency  to  involve  several  organs.  In  one  case  the  liver 
and  spleen  were  the  principal  seats,  the  lungs  and  intestine  were 
also  involved.  The  liver  was  enlarged  to  twice  the  normal  size,  of 
very  light  color  and  mottled.  Throughout  its  surface  and  within 
its  parenchyma  were  whitish  lymphomatous  deposits  of  varying 
diameters.  A  section  shows  the  liver  tissue  only  partly  obliterated 
as  a  result  of  a  filling  up  of  the  interacinous  capillaries  with  leucocytes. 
The  spleen  was  about  the  size  of  an  ordinary  blue  plum.  Each  lung 
contained  a  white  spherical  area,  the  size  of  a  pea  and  composed 
of  hyperplastic  lymphoid  tissue,  infiltrating  white  cells.  In  the  wall 
of  the  large  intestine,  involving  the  lymphadenoid  tissue,  were  round, 
slightly  raised  nodules.  In  the  second  case  the  changes  were  most 
marked  in  the  kidney  and  spleen.  The  liver,  intestine  and  heart 
were  also  involved.  The  kidneys  were  three  or  four  times  the  normal 
size  and  had  macroscopically  very  much  the  same  appearance  as  the 
liver  in  the  first  case.  The  myocardium  contained  some  small,  whitish 

*  Obviously  the  large  mononuclear  cell  of  the  classification  presented  in 
this  paper. 


Leukaemia  of  the  Fowl.     '.  ./.'•.•     ••*  "..-' :'-i3'. 

areas.  Butterfield,  in  comparing  the  histological  findings  in  Mohler's 
cases  with  his  own,  finds  a  convincing  similarity  between,  or  identity 
of,  the  infiltrating  cells.  In  Mohler's  cases,  the  infiltration  was  more 
diffuse  and  not  so  regularly  arranged  about  the  portal  tissue.  Above 
all,  the  white  blood  cells  were  markedly  increased  in  all  the  blood- 
vessels, from  the  intraacinar  capillaries  to  the  largest  veins.  The 
predominating  white  cell  was  indistinguishable  from  the  cells  in  the 
tumor  masses  of  both  these  and  Butterfield's  cases.  From  the  fore- 
going, Butterfield  felt  justified  in  granting  "the  existence  of  a 
leuksemic  and  aleukaemic  lymphadenoid  hyperplasia  in  hens." 

Butterfield  and  Mohler  deserve  the  credit  of  showing  that  leukaemia 
occurs  in  the  fowl.  Their  studies  were  limited  to  post-mortem 
findings. 

To  Warthin,8  in  1907,  we  are  indebted  for  the  first  complete  study 
of  this  disease  in  fowls.  He  had  the  good  fortune  to  secure  a  living 
animal,  which  he  kept  under  observation  for  two  and  a  half  months 
before  it  died.  During  this  time  he  had  an  opportunity  of  care- 
fully studying  the  clinical  course.  The  blood  showed  a  great  reduction 
in  the  total  number  of  red  blood  cells.  These  varied  greatly  in 
size  and  shape,  and  contained  less  haemoglobin  than  normal.  The 
total  number  of  white  cells  was  greatly  increased.  Differential  counts 
showed  a  striking  increase  of  the  "  large  lymphocyte "  at  the  ex- 
pense of  the  other  cells  of  the  normal  blood.  Numerous  mononuclear 
forms  of  the  eosinophiles,  cells  abnormal  to  the  blood,  were  seen. 
From  the  blood  changes  Warthin  felt  justified  in  making  a  diagnosis 
of  "  lymphatic  leukaemia  of  the  large  cell  type."  A  careful  autopsy 
revealed  the  following  findings:  The  liver  was  greatly  increased 
in  size  and  was  pale  yellow  in  color.  The  spleen  and  kidneys  were 
also  enlarged;  both  showed  numerous  yellowish  spots  from  pin- 
point to  pin-head  in  size.  In  the  haemorymph  nodes  small  yellowish 
nodules  were  found.  The  bone-marrow  appeared  as  solid  plugs,  red- 
dish-yellow and  friable.  The  tissue  changes  were  summarized  as 
follows:  (1)  Tumor-like  nodules  and  infiltrations  of  lymphoid  cells 
in  all  the  organs,  particularly  in  the  liver,  spleen,  kidneys,  bone- 
marrow  and  haemolymph  nodes ;  (2)  replacement  of  the  normal  white 
cells  of  the  blood  by  cells  of  the  large  lymphocyte  type,  more  or  less 
atypical  in  character,  but  identical  with  cells  in  the  tumor  masses. 
From  the  findings,  both  in  the  blood  and  in  the  tissue,  Warthin  made 
the  diagnosis  of  leukaemic  lymphocytoma. 


4  Harry  C.  Schmeisser. 

He  likewise  examined  the  material  from  two  additional  cases  of 
lymphadenoid  tumors  of  the  fowl.  One  proved  to  be  of  the  aleukaemic 
type,  as  described  by  Butterfield ;  the  other  was  of  the  leukaemic  form, 
as  described  above.  The  histological  picture,  apart  from  the  increase 
of  white  cells  in  the  blood-vessels  in  the  one  case,  was  identical  in 
both  cases  and  also  with  that  in  the  cases  given  above  (Butterfield's, 
Mohler^s  and  Warthin's).  From  these  cases  Warthin  concludes,  there- 
fore, that  there  occurs  in  the  common  fowl  a  condition  of  disseminated 
lymphocytoma,  sometimes  aleukaemic,  at  other  times  associated  with 
an  increase  of  the  white  cells  of  the  blood,  this  increase  consisting  in 
the  appearance  of  great  numbers  of  cells  of  the  large  lymphocyte  type 
and  apparently  identical  with  the  lymphoid  cells  of  the  tumor  nodules. 
He  also  regards  the  aleukaemic  and  leukaemic  conditions  as  genetically 
related,  if  not  actually  one  and  the  same  process  in  different  stages. 
Both  conditions,  he  thinks,  are  in  all  respects  analogous  to  the  similar 
ones  existing  in  man. 

The  preceding  cases  appear  to  be  very  similar  to  those  reported  by 
later  investigators  and  designated  by  them  as  splenomedullary  in 
type. 

Kon4  in  1907,  after  the  appearance  of  Warthin's  article,  reported 
what  he  considers  a  true  case  of  leukaemic  disease  of  the  chicken. 
The  gross  and  microscopical  changes,  which  were  studied  and  reported 
in  great  detail,  are  in  general  identical  with  those  of  the  cases  above. 
In  addition,  he  found  giant  cells,  though  only  a  few,  in  the  bone- 
marrow,  and  mitoses  in  the  basophiles  as  well  as  in  the  eosinophiles 
in  the  kidneys.  Because  of  the  lack  of  smears,  he  determined  the 
ratio  W/E  and  made  differential  counts  from  sectioned  blood-vessels 
of  the  liver.  He  found  that  the  white  cells,  as  compared  with  the 
reds,  were  greatly  increased  and  that  the  large  mononuclear  was  the 
predominating  cell  of  the  whites.  Mitoses  of  this  cell  were  observed. 
The  evidence  given,  he  thinks,  is  sufficient  to  consider  this  a  case  of  true 
leukaemia.  Because  of  the  enormous  swelling  of  the  spleen  and  the 
plentiful  occurrence  of  the  characteristic  cell  in  the  pulp  of  the  normal 
spleen  and  to  a  lesser  degree  in  the  normal  bone-marrow,  and  in  the 
absence  of  lymphatic  swelling  and  the  occurrence  of  this  cell  in  the  nor- 
mal lymph  tissue,  it  seems  to  him  most  likely  that  this  is  a  case  of  true 
"  splenic  leukaemia." 

Soshestrenski,"  in  May,  1908,  reported  a  case  of  spontaneous 
leukemia  of  the  fowl,  very  similar  to  the  case  described  by  Kon. 


Leukcemia  of  the  Fowl.  5 

His  study  was  limited  to  gross  and  microscopical  findings  at  autopsy. 
The  bone-marrow  was  omitted.  The  contents  of  the  blood-vessels 
of  the  organs  were  found  to  be  leukaemic.  He  designates  the  case 
also  as  "  splenic  leukaemia,"  but  in  so  doing  he  calls  attention  to  the 
fact  that  the  process  involves  many  of  the  other  organs  and  appears 
to  be  only  primary  and  most  marked  in  the  spleen.  There  was 
no  enlargement  of  the  lymph-glands. 

With  Ellermann  and  Bang,87  in  1908,  the  subject  takes  on  a 
different  phase.  Up  to  this  time,  the  communications  dealt  entirely 
with  the  recording  of  spontaneous  cases  of  leukaemia  in  the  fowl. 
Ellermann  and  Bang  were  the  first  to  successfully  transmit  the 
disease  by  experimental  inoculations  from  a  spontaneous  case  to 
other,  healthy,  fowls.  .  In  fact,  they  claim  to  have  been  the  first  to 
successfully  produce  the  disease  experimentally  in  any  animal.  They 
report  the  findings  in  two  typical  spontaneous  cases  giving  identical 
pictures.  The  blood  study  during  life  was  found  to  be  practically 
the  same  as  that  of  Warthin's  case,  with  the  exception  that  the  large 
mononuclears  frequently  contained  in  their  cytoplasm  many  granules, 
and  thus  represented  cells  which  are  not  found  in  the  normal  blood — 
myelocytes.  Small  granules  alternated  with  very  large  ones.  The 
autopsy  showed  an  enlarged  spleen  and  liver,  the  latter  with  white 
dots  and  streaks.  The  bone-marrow  was  gray-red.  The  other  organs 
presented  nothing  of  interest.  The  microscopical  changes  were  very 
similar  to  those  of  Warthin's  case.  The  experimental  leukaemia  they 
transmitted  to  the  third  generation,  producing  a  blood  picture  and 
organic  findings  identical  with  those  of  the  spontaneous  cases. 

Pseudoleukaemia,  which  is  characterized  by  the  same  organic  lesions 
as  are  found  in  true  leukaemia,  but  in  which  the  blood  picture  is 
normal,  they  found  to  occur  spontaneously  among  chickens.  They 
received  from  the  same  flock,  at  the  same  time,  a  leukaemic  and 
pseudoleukaemic  animal.  From  the  pseudoleukaemic  animal,  by  inocu- 
lation, they  produced  a  leukaemic  animal,  and  conclude,  therefore, 
that  the  leukaemia  and  pseudoleukaemia  of  chickens  are  etiologically 
identical. 

Multiple  sarcomatosis  of  the  peritoneum  occurs  epidemically  in  the 
fowl.  They  consider  this  a  manifestation  of  leukaemia,  because  by 
inoculation  from  such  a  case  they  produced  an  atypical  leukaemia  and 
carried  this  to  the  second  generation. 

They  were  successful  in  two  out  of  five  inoculations  with  a  filtrate 
from  an  emulsion  passed  through  a  "  Kerze  aus  Inf usorierde  "  and 


6  Harry  C.  Schmeisser. 

conclude,  therefore,  that  a  cell-free  filtrate  is  effective  and  that  the 
cause  must  be  an  organized  virus. 

In  the  same  year,  Ellermann  and  Bang 8  reported  that  the  blood  of 
leukaemic  fowls  contained  the  virus.  They  also  showed  that  among 
transmitted  cases  the  disease  may  appear  as  a  typical  leukemia  or  as 
a  pseudoleukaemia,  or  only  as  an  anaemia  with  changes  in  the  bone- 
marrow.  The  injection  of  five  animals  with  a  Berkefeld  filtrate  re- 
sulted in  one  early  leukemia.  The  injected  fowls  were  isolated  and 
great  care  was  exercised  during  the  experiment. 

The  following  year,  1909,  Ellermann  and  Bang, 10  reported  the 
transmission  of  the  disease  into  the  sixth  generation,  and  also  an  addi- 
tional positive  Berkefeld  filtrate  series.  Because  the  disease  can  be 
produced  by  a  cell-free  filtrate,  they  conclude:  (a)  Leukemia  must 
be  an  infectious  disease;  (b)  it  is  to  be  placed  among  the  diseases  due 
to  a  filterable  virus.  They  call  attention  to  the  fact  that  mitoses  in 
the  blood  are  pathological  and  always  present  in  leukaemia. 

Schriddle,11  in  1909,  was  the  first  to  question  whether,  in  leukaemia, 
we  are  really  dealing  with  an  infectious  etiology.  Basing  his  con- 
clusions upon  experimental  work,  he  claims  that  chickens,  injected 
with  extracts  of  entirely  normal  organs,  present  the  same  changes 
as  Ellermann  and  Bang  have  reported  for  leukaemia.  He  thinks  that 
their  findings  are  not  leukaemic  and  that,  therefore,  there  is  no  proof 
in  favor  of  the  infectious  etiology  of  this  disease. 

Hirschfeld  and  Jacoby12  in  1909,  report  a  spontaneous  case  of 
leukaemia  showing  changes  in  the  blood  and  organs  which,  they  claim, 
agree  entirely  with  the  description  of  Ellermann  and  Bang.  In  a 
second  case,  the  blood  picture,  although  not  typical,  appeared  to 
them  leukaemic.  At  autopsy  this  fowl  showed  a  typical  chicken  tuber- 
culosis. They  succeeded  in  transmitting  this  tuberculosis,  in  asso- 
ciation with  the  apparently  leukaemic  blood  picture,  into  the  fourth 
generation.  They  did  not  know  whether  they  were  dealing  with 
a  combination  of  tuberculosis  and  leukaemia  in  the  same  animal,  or 
with  pure  tuberculosis.  An  animal  injected  with  a  pure  culture  of 
the  chicken  tubercle  bacillus  developed  a  blood  picture  identical  with 
that  of  the  second  spontaneous  case.  Therefore  it  seems  highly  prob- 
able that  this  case  may  have  been  one  of  pure  tuberculosis.  At  any 
rate,  it  cannot  be  accepted  as  a  definite  and  pure  case  of  leukaemia. 

The  following  year  (1910)  the  same  authors14  report  the  injection 
of  fowls  subcutaneously  from  their  first  spontaneous  case.  They 


Leukaemia  of  the  Fowl.  7 

obtained  no  takes  and  their  strain  died  out.  From  a  leukaemic  animal 
given  to  them  by  Ellermann  and  Bang,  they  transmitted  the  disease 
into  the  fifth  generation,  obtaining  both  leuksemic  and  pseudoleukaemic 
cases.  In  the  blood,  they  found  normoblasts  and  megaloblasts,  i.  e. 
small  and  large,  round,  nucleated,  mostly  polychromatophilic  red  blood 
cells.  Although  they  state  that  the  disease  begins  in  the  bone- 
marrow,  they  leave  it  an  open  question  whether  in  the  chicken  one 
is  dealing  with  a  myeloid  or  a  lymphoid  leukaemia. 

Burckhardt,15  in  1910,  advanced  the  theory,  based  upon  investiga- 
tions of  his  own  on  transmissible  chicken  leukaemia,  that  a  particular 
leuksemic  virus  does  not  exist,  and  that  in  the  so-called  chicken 
leukaemia  one  is  very  probably  dealing  with  a  very  chronic  chicken 
tuberculosis.  As  proof,  he  claims  that  with  a  pure  culture  from  such 
an  animal  (leukaemic)  and  also  with  older  pure  cultures  of  chicken 
tubercle  bacilli,  one  can  produce  the  same  blood  picture  described  by 
Ellermann  and  Bang  for  chicken  leukaemia.  The  anatomical  findings, 
he  states,  likewise  correspond.  Gratz u  suggested  that  possibly  in 
the  culture  of  chicken  tubercle  bacilli  from  the  leukaemic  animal,  there 
may  have  been  cultivated,  in  addition  to  the  tubercle  virus,  also  the 
virus  of  leukaemia.  Friedberger16  considered  this  objection  invalid, 
because,  as  he  claimed,  one  could  produce  the  leukaemic  blood  picture 
also  by  using  old  laboratory  tubercle  cultures. 

Burckhardt,1*  in  1912,  still  adheres  to  his  theory,  but  admits  that 
he  is  unable  ever  to  bring  the  blood  into  a  leukaemic  condition  by 
inoculating  with  tubercle  bacilli. 

Hirschfeld  and  Jacoby"  in  the  same  year  inform  us  that  they 
presented  to  Burckhardt  and  Friedberger  the  chicken  with  which 
these  investigators  started  their  transmissions,  and  that  on  the  day 
of  delivery  it  showed  a  pronounced  leukaemic  blood  picture.  The 
animal,  in  addition,  surely  had  tuberculosis,  because  all  the  transmitted 
leukaemic  animals  of  the  stock  from  which  this  animal  originated 
had  tuberculosis.  They  feel  confident  that  in  Burckhardt  and  Fried- 
berger's  stock  the  tuberculosis  had  crowded  out  the  leukaemia,  until 
finally  only  tuberculous  and  not  leukaemic  animals  were  obtained.  They 
had  a  similar  experience  with  the  stock  from  which  Burckhardt  and 
Friedberger's  animal  originated. 

Against  the  existence  of  an  etiological  relationship  between  tuber- 
culosis and  leukaemia,  they  present  the  following  arguments :  (1)  The 
blood  picture  in  tuberculosis  is  never  to  be  confused  with  that  of 


8  Harry  C.  Schmeisser. 

leukaemia.  It  is  characterized  by  a  hyperleucocytosis  due  to  the 
polyniorphs.  (Ellermann  and  Bang10  had  also  stated  this  fact  at  an 
earlier  date.)  (2)  The  organs  of  the  tuberculous  chickens  were  entirely 
free  from  the  changes  which  Ellermann  and  Bang,  and  they  themselves, 
found  to  be  characteristic  of  leukaemia  and  which  correspond  entirely 
with  leukaemic  lesions  in  man.  (3)  By  injections  of  organic  emulsions 
obtained  from  spontaneous  tuberculous  chickens,  or  of  pure  cultures 
of  chicken  tubercle  bacilli,  they  uniformly  produced  a  typical  tuber- 
culous blood  picture  and  organic  changes,  always  without  any  signs 
of  leukaemia. 

Ellermann 18  u  in  1913  and  1914,  in  answer  to  the  question  whether 
this  chicken  disease  is  really  leukaemia,  shows  that  it  has  all  the 
symptoms  of  human  leukaemia.  He  meets  Schridde's  objection  by  the 
argument  that  this  investigator's  claim  was  limited  to  the  blood  picture, 
and  in  the  absence  of  the  characteristic  organic  changes,  of  which  he 
makes  no  mention,  his  experiments  are  of  no  importance.  The  in- 
jection of  an  organic  emulsion  Ellermann  never  found  to  cause  any 
change  in  the  blood,  provided- the  material  was  not  virulent.  Ellermann 
and  Bang  had  previously  produced  the  disease  with  Berkefeld  nitrates 
in  three  different  experiments.  In  this  paper  Ellermann  reports  two 
more  successful  series.  All  other  investigators  have  had  only  negative 
results.  Thus,  Hirschf eld  and  Jacoby  "  were  unsuccessful  in  two  experi- 
ments and  Burckhardt "  in  one. 

Ellermann  is  convinced  that  the  filtrate  experiments  prove  the 
theory  of  infection,  for  all  the  cells  were  surely  removed.  He  feels 
that  the  fact  that  the  virus  passed  through  a  rather  thick-walled  Berke- 
feld filter  demonstrates  that  it  is  an  invisible  filtrate  virus.  He  clearly 
shows  that  the  leukaemic  virus  can  be  separated  from  the  virus 
of  tuberculosis  by  filtration  and  that,  therefore,  the  two  diseases 
are  distinct.  Starting  with  an  emulsion  of  spleen  taken  from  an 
animal,  both  leukaemic  and  tuberculous,  in  which  tubercle  bacilli  had 
been  demonstrated,  he  passed  this  through  a  porcelain  (Reichel)  filter 
and  with  the  filtrate  he  produced  leukaemia  with  complete  absence  of 
tuberculosis  in  all  the  inoculated  animals. 

Ellermann  finally  states  that  both  the  spontaneous  and  the  trans- 
mitted leukaemia  occur  in  two  types;  (a)  myeloid,  (b)  lymphatic.  In 
the  first  the  blood  is  characterized  by  the  presence  of  numerous 
myelocytes  and  transitional  cells,  occurring  in  association  with  a  pro- 
nounced myelosis  (large  deposits  of  myelocytes)  in  the  organs.  In  the 


Leukaemia  of  the  Fowl,  9 

second,  the  blood  is  characterized  by  a  predominance  of  small  and 
large  lymphocytes  (90  per  cent  of  the  total  number)  occurring  in 
association  with  a  pronounced  lymphomatosis  (numerous  infiltrations 
with  lymphoid.  cells)  of  the  organs.  Of  interest  is  the  fact  that  a 
myeloid  type  may  occur  in  one  generation  and  a  lymphatic  in  the 
next,  or  that  both  types  may  occur  in  the  same  generation.  The 
occurrence  of  both  types  in  the  same  stock  suggests  very  strongly 
that  both  forms  of  leukaemia  in  man  are  due  to  one  and  the  same 
infection. 

II.  STUDIES  ON  THE  NORMAL  FOWL. 

With  the  hope  of  making  the  findings  in  the  leukaemic  animals  more 
clear,  the  following  brief  data  of  the  normal  fowl  are  presented.  These 
are  limited  to  those  portions  of  the  body  which  are  involved  in 
leukaemia.  They  are  compiled  from  a  large  number  of  chickens. 

EXTERNAL  APPEARANCE. 

Healthy,  young,  adult  Plymouth  Eock  hen.  Comb,  featherless 
area  about  eyes,  and  wattles  bright  red.  Conjunctivae  and  buccal 
mucous  membrane  pink.  Skin  of  body  white  with  a  faint  yellow 
tint.  Well  nourished,  sides  of  sternum  covered  with  a  thick  pad  of 
tissue,  ribs  not  palpable.  Average  rectal  temperature,  42  °  C. 

BLOOD. 

The  blood  for  counting  and  smears  was  obtained  from  the  vein  under 
the  wing,  which  always  appears  to  be  well  filled.  From  a  small  needle 
puncture  the  blood  flows  under  pressure,  is  thick,  dark  red  and  clots 
quickly. 

Blood-count. — The  nuclei-containing  red  blood  cells  of  the  fowl 
make  it  practically  impossible  to  count  the  white  blood  cells  by  the 
usual  direct  method.  After  laking  the  former,  one  cannot  differ- 
entiate between  the  nuclei  of  the  two  types  of  cells.  It  was  there- 
fore necessary  to  resort  to  the  indirect  method,  t.  e.,  to  determine  the 
proportion  of  white  to  red  cells  from  a  stained  smear,  count  the  total 
number  of  cells,  both  whites  and  reds,  by  the  direct  method,  and  then 
calculate  the  total  number  of  each  present. 

The  red  blood  cells  vary  somewhat :  lowest  limit,  2,500,000 ;  highest, 
4,500,000 ;  average,  3,000,000-4,000,000  per  c.  mm.  White  blood  cells : 


10  Harry  C.  Schmeisser. 

the  extreme  limits  are  between  20,000  and  80,000  per  c.  mm.  Propor- 
tion of  whites  to  reds,  lowest  limit,  1/40;  average,  1/50-1/150. 

Haemoglobin  (Sahli). — This  shows  considerable  variation,  lowest 
limit,  45  per  cent ;  highest,  75  per  cent;  average,  60-70  per  cent. 

Blood  Smears. — Wilson's  stain  was  found  to  give  the  best  results, 
especially  when  applied  immediately  after  the  smears  were  made. 

Classification  of  blood  cells  (Fig.  1). 

Erythrocyte. 

1.  Normocyte  (a) :  Elliptical  disk.  Nucleus,  same  shape  as  cell, 
deep  blue,  slightly  picnotic.  Cytoplasm  yellow  and  glassy.  (Both  cell 
and  nucleus  uniform  in  size,  shape  and  staining). 

Blood  Platelet  (6). 

Length  of  normocyte,  width  less  than  that  of  normocyte.  Nucleus 
round,  purple,  chromatin  diffuse,  diameter  equal  to  width  of  its 
cell.  Cytoplasm  pale  gray  with  vacuoles  about  nucleus,  frequently  con- 
taining small  circumscribed  red  structures.  May  vary  in  size  and 
shape. 

Leucocytes. 

1.  Polymorphonuclear  leucocyte  with  eosinophilic  rods  (c)  :  Bound, 
diameter  about  length  of  normocyte.    Nucleus  has  two  or  more  lobes, 
pale  blue,  chromatin  diffuse.     Cytoplasm  colorless  with  bright  red, 
spindle-shaped  rods. 

2.  Polymorphonuclear  leucocyte  with  eosinophilic  granules    (d)  : 
About  the  same  in  shape  and  size.    Nucleus  has  two  or  more  lobes, 
purple,   slightly   picnotic.      Cytoplasm   faintly   blue   with   dull   red 
granules. 

3.  Lymphocyte  (e,  e') :  Round,  diameter  about  width  of  normocyte. 
Nucleus  round,  purple,  chromatin  diffuse.    Cytoplasm  small  in  amount, 
to  one  side  of  nucleus,  pale  blue.    Same  cell  may  be  slightly  larger. 
Thus  a  division  into  the  small  (e)  and  large  (e')  lymphocyte  may  be 
made. 

4.  Large  mononuclear  cell    (/)  :  Round  or  oval,  diameter  about 
length  of  normocyte  (at  times,  more  or  less).    Nucleus  round,  oval  or 
slightly    irregular,    and    larger,    otherwise    similar    to    nucleus    of 
lymphocyte.    Cytoplasm  abundant,  completely  surrounds  nucleus,  pale 
blue.     (A  suggestion  of  fine  granules.) 


Leukaemia  of  the  Fowl.  11 

5.  Mast  cell  (g)  :  About  same  size  and  shape.  Nucleus  round  or 
oval,  very  pale  blue.  Cytoplasm  abundant,  colorless,  mostly  to  one 
side  of  nucleus  with  purple  granules,  some  scattered  over  nucleus. 

Differential  Count,  300  Cells. 

Per  cent. 

Polymorphonuclear  with  eosinophilic  rods 29.6 

Polymorphonuclear  with  eosinophilic  granules 4.3 

Lymphocyte   42.3 

Large  mononuclear  cell 19.4 

Mast  cell 2.2 

Unclassified  cells 2.2 


100.0 
AUTOPSY  PROTOCOL. 

The  following  findings  would  correspond  to  those  in  a  fowl  of  the 
average  size  and  weight  (1760  gm.)  of  the  animals  injected. 

Subcutaneous  Fat  Abundant  (Fig.  4).  Thick  muscle  pad  covering 
the  skeleton  (Fig.  4).  Inner  surface  of  skin  slightly  yellow. 

Cervical  Lymph-glands  *  (Figs.  3,  a  and  b).  Sometimes  difficult  to 
find.  Present  as  two  chains,  each  consisting  of  six  to  ten  glands, 
one  on  each  side  of  neck,  lying  upon  the  internal  jugular  vein,  buried 
in  fat,  and  extending  from  the  middle  of  neck  to  base  of  heart.  They 
are  delicate,  elliptical,  flat,  lobulated  bodies,  averaging  1  x  .5  x  .2  cm. 
The  parenchymatous  lobules  are  pink  and  separated  from  each  other 
by  narrow  septa  of  fat.  No  other  lymph-glands  were  found  in  the 
entire  body. 

Thyroids  and  Parathyroids. — Two  of  each  gland.  The  thyroid,  a 
dark  red,  translucent,  spindle-shaped  body,  1  x  .4  x  .4  cm.,  with 
just  visible  colloid-filled  acini,  separated  by  delicate  gray  septa.  The 
parathyroid  is  attached  to  its  lower  pole.  This  is  a  small  bluish- 
white  sphere,  2  mm.  in  diameter.  Thus,  in  pairs,  they  are  found,  one 
pair  on  each  side  of  the  body,  just  above  the  heart. 

Peritoneal  Cavity  (Fig.  4). — An  omen  turn  composed  entirely  of  fat, 
1  cm.  in  thickness,  takes  its  origin  from  the  anterior  surface  and  lower 
margin  of  the  gizzard,  extending  over  coils  of  intestine,  etc.,  holding 

*  Kon  *  considers  these  structures  the  thymus.  He 4  and  Ellermann  M  " 
state  that  the  fowl  has  no  lymph-glands.  Soshestrenski 5  asserts  their 
existence  by  stating  that  in  his  case  they  were  not  enlarged. 


12  Harry  C.  Schmeisser. 

them  against  the  posterior  peritoneal  wall.  It  is  fastened  to  the 
parietal  peritoneum,  laterally,  and  at  the  pubis.  The  lower  margins  of 
the  right  and  left  lobes  of  the  liver  extend  down  between  the  sternum 
and  omentum  to  within  3  cm.  of  the  tip  of  the  xiphoid. 

Liver  (Fig.  4). — The  first  organ  which  presents  itself  on  removing 
the  sternum.  Eight  lobe  measures  7.5  x  4.5  x  2  cm. ;  left  lobe,  6.5  x  5  x  2 
cm.  Total  weight  50  gm.  or  2.8  per  cent  of  body  weight.  Uni- 
formly reddish  brown  with  smooth  and  glistening  surface,  soft  and 
friable.  Lobule  about  pin-head  in  size,  center  darker  than  periphery ; 
usually  distinct,  at  times  difficult  to  see.  The  cut  surface  shows  small 
blood-vessels  on  cross  and  longitudinal  section.  The  lobulation  is  less 
readily  seen. 

Spleen  (Fig.  6). — Lies  just  behind  the  liver.  Measures  2  x  1.5  x  1 
cm.,  weighs  1  gm.,  or  .05  per  cent  of  body  weight.  It  is  small,  soft, 
reddish  brown.  Beneath  its  smooth  and  glistening  capsule,  may  be 
seen  bluish  white  Malpighian  bodies,  slightly  larger  than  pin-points,  at 
times  indistinct.  On  section,  the  capsule  appears  very  delicate; 
trabeculse  are  few,  but  usually  definite,  containing  gaping  blood-vessels. 
Malpighian  bodies  at  times  are  prominent.  Pulp  does  not  rise  above 
edge  of  capsule. 

Heart. — Lies  within  a  delicate,  transparent  pericardium,  containing 
a  small  amount  of  clear  serum.  Myocardium  is  uniformly  reddish 
brown. 

Lungs. — Bright  red  and  of  a  characteristic  construction,  consisting 
of  a  mass  of  entwined  air  tubules  with  large  lumina  and  spongy  walls, 
separated  from  each  other  by  a  small  amount  of  vascular  connective 
tissue.  On  section,  this  construction  becomes  more  pronounced.  The 
wall  of  each  air  tubule  projects  as  a  pale  ridge,  separated  from  its 
neighbor  by  a  red  linear  depression,  in  which  blood-vessels  are  common. 

Gastro-intestinal  Tract,  Pancreas  and  Adrenals. — These  are  of  little 
interest  except  that  beneath  the  serosa  of  the  lower  half  of  the  intestine 
are  frequently  seen  pearly  nodules,  less  than  a  pin-head  in  size. 

Mesentery. — A  delicate,  cobweb-like  membrane  with  some  fat,  but 
no  demonstrable  lymph-glands. 

Sidneys. — Measure  6.5  x  1.7  x  1  cm.,  and  weigh  together  12  gm.,  or 
7  per  cent  of  body  weight.  They  are  uniformly  reddish  brown  with  a 
slightly  nodular  surface. 

Bone-marrow. — Taken  from  long  bones  of  upper  and  middle  third 
of  leg.  It  is  very  soft,  semifluid,  bright  red,  mottled  with  yellow,  i.  e.} 


Leukaemia  of  the  Fowl,  13 

rich  in  red  blood  cells  and  fat.  Lower  part  of  middle  third  frequently 
consists  of  a  solid,  yellow  column  of  fat.  The  marrow  cavity  may  be 
almost  occluded  by  bony  septa. 

MICEOSCOPICAL     EXAMINATION. 

Cervical  Lymph-gland. — Section  shows  lobules  of  parenchyma, 
separated  by  fatty  tissue.  Each  lobule  is  surrounded  by  a  delicate 
fibrous  capsule  and  contains  a  very  fine  reticulum,  in  which  the 
lymphocyte  is  diffusely  scattered.  This  is  a  small,  round  cell  with  a 
round,  deeply  staining,  picnotic  nucleus,  usually  incompletely  sur- 
rounded by  a  narrow  rim  of  pink  cytoplasm.  Sometimes  red  blood 
cells  are  associated  with  the  lymphocyte,  but  mostly  they  are  confined 
to  and  form  the  sole  occupants  of  the  numerous  capillaries.  They 
appear  as  elongated,  yellowish-pink  cells,  with  a  solid  black  rod  or  dot 
for  nucleus,  according  to  whether  this  is  seen  in  longitudinal  or  cross 
section.  Scattered  through  the  lobule  are  small,  sharply  outlined, 
hyaline  structures,  which  Kon  4  considered  as  corresponding  to  Hassall's 
corpuscles  of  the  thymus. 

Thyroid. — Consists  of  polyhedral  acini,  which  vary  in  size,  are  lined 
with  cubical  epithelium  and  filled  with  granular  colloid.  They  are 
separated  from  each  other  by  a  small  amount  of  fibrous  tissue,  rich 
in  blood  capillaries.  Sometimes  accumulations  of  lymphocytes  may  be 
seen  near  the  larger  vessels. 

Parathyroid. — Within  its  capsule  is  seen  a  prominent  reticulum  filled 
with  closely  packed  cells,  whose  nucleus  is  round  or  oval,  semivascular 
and  larger  than  that  of  the  lymphocyte. 

Liver. — The  lobule  is  difficult  to  limit.  Periportal  spaces  are  not 
easy  to  find.  They  consist  of  one  or  several  arteries,  a  vein,  one  or 
several  gall-ducts,  and  very  little  or  practically  no  fibrous  tissue,  usually 
free  from  infiltrated  cells,  although  lymphocytes  may  be  present  dif- 
fusely or  in  small  follicles.  The  liver  cells  are  arranged  in  trabeculae, 
separated  by  capillaries.  All  blood-vessels  and  capillaries  are  filled 
exclusively  with  red  blood  cells. 

Spleen. — The  Malpighian  bodies  are  indistinct,  numerous,  closely 
packed,  composed  of  masses  of  lymphocytes  surrounding  very  small 
arteries.  Bed  blood  cells  are  limited  to  the  pulp,  where  they  occur 
more  or  less  in  clusters,  although  one  is  unable  to  demonstrate  sinuses 
or  inclosures  of  any  kind.  The  lymphocytes  are  also  diffusely  scattered 
throughout  the  pulp.  Veins  tend  to  be  rich  in  lymphocytes  and 
poor  in  red  blood  cells ;  the  artery  shows  the  opposite  picture. 


14  Harry  C.  Schmeisser. 

Lung. — Presents  a  characteristic  structure,  entirely  different  from 
that  in  the  human  lung.  The  tubules  mentioned  in  the  macroscopical 
description  are  seen  in  cross,  oblique,  or  longitudinal  section,  forming 
large  polyhedral  units  with  wide  walls  composed  of  capillaries.  The 
intercapillary  air  spaces  communicate  with  each  other  and  with  a  large 
central  lumen.  The  latter  is  lined  with  a  narrow  band  of  smooth 
muscles  surmounted  by  endothelium,  frequently  cuboidal.  The  inter- 
tubular  fibrous  tissue  is  small  in  amount,  and  contains  large  blood- 
vessels, whose  branches  extend  into  the  capillary  bed.  These  structures 
are  closely  packed  with  red  blood  cells.  Only  occasionally  does  one  see  a 
lymphocyte.  The  bronchi  resemble  those  of  the  human  lung.  Follicles 
of  lymphoid  cells  are  frequently  found  in  the  submucosa  or  outside  of 
the  bronchi  near  arteries. 

Bone-marrow. — A  low-power  picture  is  very  similar  to  human  resting 
marrow,  i.  e.}  one  sees  a  framework  of  fatty  tissue  inclosing  nests  of 
marrow  cells.  Arteries  are  filled  solely  with  red  blood  cells.  Venous 
spaces  are  difficult  to  determine.. 

Classification  of  Marrow  Cells. — Very  thin  paraffin  sections  were 
stained  with  haematoxylin  and  eosin  and  studied  under  the  oil- 
immersion  lens.  The  same  cells  appear  slightly  different  under  these 
conditions  than  when  seen  in  the  Wilson  smears  of  normal  and  leukaemic 
blood. 

Erythrocytes. 

1.  Normocyte  (a) :  Elongated,  varying  in  shape,  due  to  pressure. 
Nucleus  a  solid,  black  rod  or  dot   (longitudinal  or  cross  section). 
Cytoplasm  yellowish-pink  and  glassy. 

2.  Normoblast  (6)  :  Eound,  diameter  about  width  of  normocyte. 
Nucleus  round,  uniformly  black.    Cytoplasm  pink  or  faintly  blue,  and 
glassy.    Frequently  a  narrow  clear  zone  is  seen  about  the  nucleus. 

3.  Megaloblast  (6) :  Same,  larger,  about  length  of  a  normocyte. 
Nucleus  slightly  picnotic. 

Leucocytes. 

1.  Polymorphonuclear  myelocyte  with  eosinophilic  rods  *  (c) : 
Round,  Nucleus,  two  or  more  solid  black  lobes.  Cytoplasm  colorless 
with  bright  red,  spindle-shaped  rods. 

*  These  are  obviously  the  polymorphonuclear  with  eosinophilic  rods,  the 
polymorphonuclear  with  eosinophilic  granules  and  the  large  mononuclear 
cell  of  the  normal  blood. 


Leukaemia  of  the  Fowl.  15 

2.  Polymorphomiclear  myelocyte  with  eosinophilic  granules  *  (6)  : 
Round,  about  same  size.   Nucleus  has  two  or  more  slightly  vesicular 
lobes.    Cytoplasm  colorless  with  bright  red  granules. 

3.  Mononuclear  myelocyte  with  eosinophilic  granules  (a)  :   Round, 
or  oval,  varying  in  size,  mostly  larger  than  1  and  2.    Nucleus  round, 
oval,  or  horseshoe-shaped,  eccentric,  slightly  or  very  vesicular.    Cyto- 
plasm colorless  with  bright  red  granules. 

4.  Large  mononuclear  myelocyte  *    (d)  :   Round,   slightly  larger. 
Nucleus  round,  very  vesicular,  one  or  more  nucleoli.    Cytoplasm  baso- 
philic,  moderate  in  amount. 

Reticular  Cell. — Branched.  Nucleus  elongated,  vesicular,  several 
nucleoli.  Cytoplasm  pink,  giving  off  delicate  fibers  to  form  reticulum. 

Lymphocytes,  mast  cells,  platelets,  mitoses  of  red  and  white  cells 
were  not  seen.  Letters  in  (  )  =  order  of  predominance. 

Heart,  Pancreas  and  Kidney :  For  all  practical  purposes  similar  to 
the  human. 

III.  A   CASE   OF   SPONTANEOUS   LEUKEMIA. 

On  October  31,  1912,  a  typical  case  of  leukaemia  of  the  fowl  was 
brought  to  the  pathological  laboratory.  The  animal,  a  Plymouth  Rock 
hen,  had  just  been  killed,  and  its  body  was  still  warm.  Nothing  is 
known  of  its  clinical  history.  An  abstract  of  the  findings  is  here 
given. 

BLOOD. 

The  study  of  the  blood  was  limited  to  smears  taken  from  the  heart 
just  after  the  animal  had  been  received  at  the  laboratory.  They  were 
stained  by  Wilson's  method.  A  detailed  description  of  the  cells  of 
leuksemic  blood  will  be  reserved  for  the  experimental  leukaemia  where 
far  better  opportunities  for  careful  study  of  the  same  were  offered. 
Suffice  it  here  simply  to  enumerate  and  briefly  comment  upon  those 
cells  which  were  present. 

Blood  Smears.  There  was  an  enormous  increase  in  the  white  blood 
cells,  the  proportion  of  whites  to  reds  being  1 :  1.3.  The  predomina- 
ting cells  were  the  large  mononuclear  and  the  mononuclear  myelocyte 
with  eosinophilic  granules.  The  latter  is  abnormal  to  the  blood, 

*  These  are  obviously  the  polymorphonuclear  with  eosinophilic  rods,  the 
polymorphonuclear  with  eosinophilic  granules  and  the  large  mononuclear 
cell  of  the  normal  blood. 
2 


16  Harry  C.  Schmeisser. 

normal  to  the  bone-marrow,  and  when  extramedullar  is  typical  of 
leukaemia.  Lymphocytes  and  polymorphs  were  strikingly  decreased. 
Of  the  latter  those  with  red  granules  and  the  mast  cell  were  rare. 
Mitoses  of  the  large  mononuclear  were  common.  The  red  blood  cells 
appeared  to  be  poor  in  haemoglobin  and  showed  anisocytosis, 
poikilocytosis  and  polychromatophilia.  These  cytoplasmatic  changes 
were  usually  associated  with  an  increase  in  the  size  of  the  nucleus. 
Premature  red  blood  cells,  normoblasts  and  megaloblasts  were  present  in 
large  numbers. 

Differential  Count,  300   Cells. 

Per  cent. 

Polymorphonuclear  with  eoslnophilic  rods 8 

Polymorphonuclear  with  eosinophilic  granules 0 

Lymphocyte    2 

Large  mononuclear  cell 30 

Mast   cell 0 

Monuclear  myelocyte  with  eosinophilic  granules 52 

Unclassified    cells 8 

100 
AUTOPSY   PEOTOCOL. 

The  animal  was  of  medium  size ;  the  weight  was  not  taken. 

External  Appearance. — Comb,  featherless  area  about  eyes,  and 
wattles  of  an  ash  color.  Buccal  mucous  membrane  and  conjunctivas, 
very  pale.  Anterior  chamber  of  left  eye  filled  with  an  old  blood- 
clot.  Eight  eye  normal.  A  moderately  firm  slightly  nodular  tumor, 
3.7  x  2  x  1.5  cm.,  occupied  the  triangular  space  on  the  left  side  of 
head  between  the  angle  of  the  mouth,  ear  and  angle  of  the  lower  jaw, 
extending  below  the  ramus  of  the  latter.  Subcutaneous  fat  was 
practically  absent.  Emaciation  was  extreme  and  there  was  marked 
muscular  atrophy.  A  second,  slightly  smaller  tumor,  1.7  x  1  x  1  cm., 
was  found  just  inside  the  ramus  and  below  the  orbit,  apparently 
communicating  over  the  ramus  with  the  first  growth  and  continuous 
below  with  a  slightly  larger,  third  mass.* 

Cervical  Lymph-glands. — Somewhat  enlarged.  Lobulation  indis- 
tinct. 

*  A  more  detailed  description  and  study  of  these  tumors  will  be  reserved 
for  a  future  communication. 


Leukemia  of  the  Fowl.  17 

Peritoneal  Cavity. — Omental  fat  entirely  absent.  Lower  margins  of 
right  and  left  lobes  of  liver  extended  almost  to  the  pubes,  i.  e.,  far 
below  xiphoid. 

Liver. — Enormous.  Dimensions  and  weight  not  taken.  Its  surface 
was  extremely  mottled.  It  was  reddish  brown  and  specked  with 
innumerable  gray  or  slightly  yellow  spots  from  a  pin-point  to  a  few 
millimeters  in  diameter,  frequently  closely  packed  to  form  irregular 
areas,  the  largest  1  cm.  in  diameter.  In  addition  there  were  scat- 
tered gray  or  slightly  yellow  nodules,  averaging  about  2  mm.  in 
diameter.  Sectioned  surface  similar  in  appearance.  The  blood-vessels 
were  surrounded  by  a  gray  zone. 

Spleen. — Enormous.  Dimensions  and  weight  not  taken.  It  was 
about  the  size  of  a  small  hen's  egg.  Diffusely  gray. 

Heart. — At  the  apex  there  were  several  gray  spots,  pin-point  in  size. 

Kidneys. — Greatly  enlarged.  Both  showed  nodules,  similar  to  those 
in  liver. 

Bone-marrow. — Abundant,  gray,  with  absence  of  fat. 

Thyroids,  Parathyroids,  Lungs,  Gastro-intestinal  Tract,  Pancreas 
and  Adrenals. — Apparently  uninvolved. 

MICROSCOPICAL .  EXAMINATION. 

Cervical  Lymph-glands. — The  normal  structure  was  somewhat 
changed.  There  was  complete  disappearance  of  the  interlobular  fat 
with  approximation  of  the  greatly  swollen  parenchymatous  lobules. 
Here  and  there  were  intra-  and  inter-lobular  foci  of  myeloid  tissue. 
These  frequently  enclosed  an  artery  or  vein.  There  was  also  a  more 
diffuse  infiltration  of  the  parenchyma  by  myeloid  cells,  filling  capillaries, 
veins,  arteries  and  in  places  breaking  through  the  lobular  capsule  into 
the  interlobular  tissue.  Of  the  infiltrating  cells  two  predominated :  (1) 
A  large  mononuclear,  usually  round,  at  times  slightly  polygonal  due  to 
pressure,  with  a  single,  round,  oval,  or  indented,  vesicular,  at  times 
multiple,  nucleus  with  one  or  more  nucleoli.  Its  cytoplasm  was  non- 
granular  and  slightly  basophilic.  (2)  The  mononuclear  myelocyte 
with  eosinophilic  granules,  described  under  normal  bone-marrow. 
Mitoses  of  these  two  cells  were  quite  common.  Normoblasts  and 
megaloblasts  appeared  to  be  present. 

Liver. — Here  the  process  was  most  extreme.  Very  little  liver  tissue 
remained.  Everywhere  were  closely  packed  masses  of  myeloid  cells 
from  which  the  liver  trabeculae  had  completely  disappeared.  These 


18  Harry  C.  Schmeisser. 

masses  of  cells  surrounded  blood-vessels,  both  arteries  and  veins,  infil- 
trating the  walls  of  the  latter  and  filling  the  lumina  of  both.  Within 
the  vessels  the  white  blood  cells  were  present  in  about  equal  proportion 
with  the  red  blood  cells.  Between  these  more  focal  accumulations  the 
myeloid  cells  had  infiltrated  in  a  more  diffuse  manner  between  the  liver 
columns,  spreading  them  apart.  It  was  usually  difficult  to  demonstrate 
the  capillary  wall.  Hepatic  cells  in  these  locations  did  not  suffer  so 
much.  Some  of  the  above-mentioned,  circumscribed  infiltrations 
showed  a  coarse  sclerosis.  The  same  infiltrating  cells  were  present  as 
in  the  cervical  lymph-glands,  with  a  prevalence  of  the  large  mononu- 
clear,  which  was  very  rich  in  mitoses,  and  the  mononuclear  myelocyte 
with  eosinophilic  granules.  The  two  types  of  polymorphonuclear  cells 
and  the  premature  red  blood  cells  were  present  in  fewer  numbers. 

Spleen. — Pulp  diffusely  infiltrated  with  closely  packed  leukaemic 
cells,  which  crowded  the  reticulum,  distended  the  blood-vessels  and 
separated  and  compressed  the  Malpighian  bodies.  The  mononuclear 
myelocyte  with  eosinophilic  granules,  although  present,  was  scarce. 
The  large  mononuclear,  frequently  showing  mitoses,  was  the  common 
cell. 

Heart. — The  intramuscular  capillaries,  were  moderately  distended 
with  the  large  mononuclears  and  red  blood  cells,  present  in  about  equal 
proportion.  The  former  had  also  infiltrated  between  the  muscle  fibers. 
The  mononuclear  myelocyte  with  eosinophilic  granules  was  only  occa- 
sionally seen,  both  within  and  without  the  blood-vessels. 

Lungs. — The  intertubular  blood-vessels,  their  branches  which  extend 
into  the  capillary  bed,  and  also  the  capillaries,  were  distended  with 
leukaemic  blood,  in  which  the  large  mononuclear  seemed  to  exceed  the 
red  blood  cell.  Mitoses  were  common.  Infiltration  of  the  tissue  was 
limited  to  two  foci  of  myeloid  cells.  The  one  was  composed  principally 
of  the  mononuclear  myelocyte  with  eosinophilic  granules  and  the  large 
mononuclear.  Mitoses,  especially  of  the  first  cell,  were  seen.  Both 
types  of  polymorphs  were  also  present.  The  other  focus  was  composed 
exclusively  of  premature  red  blood  cells,  normoblasts  and  megaloblasts 
showing  mitoses. 

Kidneys. — All  the  blood-vessels,  from  the  largest  to  the  capillaries  of 
the  glomerular  tuft,  were  distended  with  the  characteristic  leukaemic 
blood.  Throughout  the  section  there  was  a  diffuse  infiltration  of 
myeloid  cells,  especially  between  the  convoluted  tubules.  Here  and 
there  were  foci,  in  some  of  which  the  mononuclear  myelocyte  with 


Leukaemia  of  the  Fowl.  19 

eosinophilic  granules  predominated,  frequently  showing  mitoses ;  others 
seemed  to  be  composed  exclusively  of  the  large  mononuclear.  Here 
mitoses  were  also  common.  In  these  foci  the  convoluted  tubules  had 
either  been  pushed  aside  or  had  atrophied. 

Bone-marrow. — This  was  greatly  changed.  It  consisted  of  a  closely 
packed  mass  of  white  marrow  cells,  with  complete  atrophy  of  the  fat 
and  great  rarity  of  normocytes.  One  or  two  small  focal  areas  of 
sclerosis  were  present.  The  arteries  were  mostly  empty.  Some  showed 
a  little  blood  containing  a  few  large  mononuclears.  Those  marrow  cells, 
which  were  present,  both  red  and  white,  answered  to  their  descriptions 
given  under  normal  bone-marrow,  with  the  exception  of  the  large 
mononuclear  myelocyte,  which  showed  considerable  variation  in  its 
nucleus.  This  was  either  single  or  multiple,  round,  oval,  or  horseshoe- 
shaped.  The  order  of  predominance  had  changed  greatly.  The  large 
mononuclear  myelocyte  was  present  in  far  greater  numbers  than  any 
other  cell,  and  showed  extensive  mitoses.  The  normoblast  and  megalo- 
blast  with  mitoses  followed  next  in  frequency;  then  the  normocyte. 
Polymorphonuclear  myelocytes,  those  with  eosinophilic  rods  and  those 
with  eosinophilic  granules,  had  disappeared  entirely.  Curious  is  the 
fact  that  the  mononuclear  myelocyte  with  eosinophilic  granules  could 
not  be  demonstrated  with  certainty.  As  in  the  normal  marrow  lymph- 
ocytes, mast  cells  and  platelets  were  not  seen. 

Thyroids,  Parathyroids,  Pancreas  and  Adrenals. — These  were  not 
studied. 

SUMMAKY. 

In "  summarizing  the  changes  in  the  blood  and  organs,  there  was 
found : 

1.  In  the  Blood. — (a)  A  great  increase  in  the  total  number  of  white 
blood  cells.  Although  a  total  count  was  not  made,  this  increase  was 
evident  from  the  appearance  of  the  blood  smears,  and  of  the  blood- 
vessels in  sections.  The  actual  proportion  of  white  to  red  cells  sub- 
stantiated this  fact.  The  differential  count  showed  a  marked  increase 
of  the  large  mononuclear  cell  at  the  expense  of  the  other  white  blood 
cells  of  the  normal  blood.  In  addition,  a  true  myelocyte  appeared  in  the 
circulation.  Mitoses  of  the  large  mononuclear  were  common,  (b)  A 
corresponding  decrease  in  the  total  number  of  red  blood  cells.  These 
showed  a  drop  in  haemoglobin,  variation  in  size  and  shape,  basophilic 
staining  of  the  cytoplasm,  and  swelling  of  their  nuclei.  Premature 
red  cells,  normoblasts  and  megaloblasts  made  their  appearance. 


20  Harry  C.  Schmeisser. 

2.  In  the  Organs. —  (a)  A  diffuse  and  circumscribed,  at  times 
nodular,  infiltration  of  myeloid  cells,  in  which  the  large  mononuclear, 
and  mononuclear  myelocyte  with  eosinophilic  granules  predominated, 
although  the  other  cells  of  the  normal  bone-marrow  were  at  times 
present.  This  myelosis  involved  especially  the  liver,  spleen,  kidneys  and 
bone-marrow,  resulting  in  an  extreme  enlargement  of  the  first  three 
organs.  Almost  all  of  the  remaining  organs  showed  infiltrations,  but  to 
a  less  degree,  (b)  A  change  in  the  contents  of  the  blood-vessels.  The 
proportion  of  white  to  red  cells  was  greatly  increased.  The  predomina- 
ting cells  were  the  same  as  those  of  the  infiltration. 

CONCLUSION. 

In  conclusion,  if  we  consider  that  the  cells,  characteristic  of  both 
leukaamic  infiltrate  and  blood,  were  the  same,  and  that  under  normal 
conditions  the  mononuclear  myelocyte  with  eosinophilic  granules 
occurs  only  in  the  bone-marrow  and  the  large  mononuclear  only  in  the 
marrow  and  blood,  it  is  evident  from  the  summarized  facts,  that  the 
above  case  must  be  considered  a  typical  case  of  myeloid  leukcemia. 

IV.  EXPERIMENTAL  LEUKEMIA. 

With  material  from  the  above  case,  the  disease  was  successfully  trans- 
mitted into  the  fifth  generation.  A  total  of  105  animals  were  used  in 
conducting  many  different  kinds  of  experiments.  Of  this  number,  22 
in  all  have  developed  leukaemia.  In  four  additional  animals,  a  definite 
diagnosis  could  not  be  established,  although  the  appearances  were  highly 
suggestive.  The  strain  has  now  been  running  for  more  than  13  months. 

This  paper  will  be  confined  to  a  report  of  those  series  which  deal  with 
simple  transmission  of  the  disease  by  the  injection  of  an  organic 
emulsion. 

Five  of  these  series  were  conducted,  each  consisting  of  5,  10  or  15 
fowls.  The  percentage  of  positives  per  series  varied  from  20-40  per 
cent.  Of  the  total  number  of  40  chickens  injected,  13  became  leukaemic, 
i.  e.  32.5  per  cent.  In  addition,  a  definite  diagnosis  could  not  be  made 
in  three,  although  the  findings  were  very  suggestive. 

PREPARATION    OF    MATERIAL,     METHODS    OF    INJECTION,    ETC. 

The  material  used  for  transmission  was  an  emulsion  of  liver,  and 
sometimes  of  spleen  also.  It  was  prepared  by  thoroughly  macerating 


Leukaemia  of  the  Fowl.  21 

pieces  of  the  organ  in  a  mortar,  after  the  addition  of  .9  per  cent  normal 
salt  solution.  This  was  filtered  through  a  single  layer  of  fine  linen  or 
a  small  amount  of  raw  cotton,  thus  removing  the  fibrous  tissue  suf- 
ficiently for  intraperitoneal  injection,  although,  when  it  was  used  in- 
travenously, instant  death  frequently  resulted.  Hence  it  was  found  best 
to  filter  also  through  two  layers  of  filter  paper  with  the  aid  of  a  suction 
pump.  This  filtrate  was  found  to  be  absolutely  fiber-free,  but  still  con- 
tained blood  and  parenchymatous  cells.  A  15  per  cent  emulsion  gave 
the  best  results.  The  entire  preceding  process,  as  well  as  the  following 
steps,  were  carried  out  aseptically. 

The  fowls  were  injected  either  intravenously  or  intraperitoneally 
with  10  cc.  Both  methods  were  sometimes  combined,  when  a  total  of 
20  cc.  was  administered.  The  vein  selected  for  injection  was  the  large 
one  under  the  wing. 

Animals  used  for  transmission  were  young,  adult  hens  of  the  same 
breed  as  the  spontaneous  case,  and  exemplified  by  the  normal  control. 

CLINICAL    HISTORY. 

Incubation  Period. — This  is  usually  from  five  to  six  weeks.  In  rare 
cases,  it  may  reach  a  maximum  of  16  weeks. 

Signs  and  Symptoms. — The  onset  is  usually  rather  abrupt,  preceded 
by  no  definite  premonitory  symptoms.  The  animal,  which  has  pre- 
viously appeared  entirely  normal,  begins  to  show  a  slight  but  progres- 
sive, at  times  a  sudden  and  intense,  pallor  of  its  comb,  the  featherless 
area  about  the  eyes  and  the  wattles.  This  is  almost  invariably  associated 
with  jaundice,  which  is  likewise  progressive  and  usually  reaches  an 
extreme  grade.  The  combination  of  intense  pallor  and  jaundice  results 
in  a  characteristic,  yellowish-pink  color,  which  gives  the  fowl  a  ghastly 
appearance.  The  comb  may  be  surprisingly  red  or  extremely  pale  with- 
out jaundice.  The  animal  emaciates  rapidly  and  to  an  extreme  degree. 
The  actual  loss  in  weight  during  the  disease  is  striking  and  best  illus- 
trated by  the  following  figures.  No.  28,  on  the  day  of  the  onset  of  the 
disease,  weighed  1484.5  gm.  The  duration  of  the  disease  was  three 
weeks,  four  days.  At  death  the  weight  was  897  gm.  Therefore,  there 
was  a  loss  of  587.5  gm.  in  25  days,  or  at  rate  of  23.5  gm.  per  day. 

At  first  the  bird  acts  entirely  normally,  or  it  may  appear  slightly  ill. 
In  a  few  days,  however,  it  acts  as  if  it  were  very  sick,  stops  eating  and 
drinking,  and  stands  about  with  head  retracted,  eyes  closed  and  tail 
drooping.  It  prefers  to  assume  a  squatting  position.  If  made  to  move 


22  Harry  C.  Schmeisser. 

it  does  so  very  slowly  and  carefully.  Weakness  becomes  more  and  more 
marked,  until  on  the  last  day  it  lies  prostrated,  with  its  head  on  the  floor, 
wings  drooping,  eyes  closed  and  at  times  is  dyspnceic. 

Fever  has  never  been  observed. 

Duration  of  the  Disease. — This  is  most  frequently  from  one  to  two 
weeks.  One  case  exceptionally  acute  lasted  only  33  hours.  Two  cases, 
three  days.  The  longest  course  was  four  weeks,  four  days. 

'Prognosis. — Having  once  begun,  the  disease  progresses  steadily  to  a 
•  fatal  issue.    Only  in  one  case  out  of  23  leukaemic  animals  did  a  spon- 
taneous cure  result. 

BLOOD. 

In  Gross. — With  the  onset  of  anaemia,  the  vein  under  the  wing  col- 
lapses and  the  blood  undergoes  a  change.  It  soon  flows  with  the  great- 
est ease  and  rapidity,  resembles  pale  yellow  water  and  shows  no  tendency 
to  clot.  The  animal  apparently  would  bleed  to  death  from  a  pin-point 
wound,  if  the  haemorrhage  were  not  artificially  arrested. 

Blood-count. — In  most  cases  there  is  a  progressive  and  extreme  de- 
crease in  the  total  number  of  red  blood  cells.  At  onset  the  count  may 
be  but  slightly  below  normal,  2,224,000,  while  just  before  death  it,  at 
times,  reaches  630,000.  More  commonly,  the  lowest  point  ranges 
between  1,112,000  and  1,408,000  per  c.  mm.  In  one  case,  the  count 
remained  normal. 

The  count  of  white  cells  is  invariably  high,  between  131,200  and 
210,000  per  c.  mm. 

Katioof  W/K=l/3-l/9. 

Haemoglobin. — This  usually  falls  steadily  and  reaches  a  very  low 
point.  From  slightly  below  normal,  40-50  per  cent  at  onset,  it  fre- 
quently drops  to  10-15  per  cent  just  before  death.  In  several  cases  it 
fell  only  to  23  per  cent.  In  one  case  there  was  no  change  at  all. 

Blood  Smears. — The  morphology  of  the  leukaemic  blood  is  excep- 
tionally interesting.  In  addition  to  the  enormous  increase  in  the  num- 
ber of  white  cells,  all  of  the  cellular  elements  show  marked  changes  and 
many  new  forms  make  their  appearance.  Smears  were  stained  by  Wil- 
son's method. 

Classification  of  blood  cells  (Fig.  2). 

Erythrocytes. 

1.  Normocyte:  (a)  Normal  (a),  except  for  variation  in  the 
amount  of  hemoglobin,  (b)  Showing  anisocytosis,  poikilocytosis  and 


Leukaemia  of  the  Fowl.  23 

polychromatophilia,  mostly  associated  with  a  swelling  of  the  nucleus 
and  separation  of  its  chromatin  (6). 

2.  Normoblast  (c)  :  Eound,  diameter  less  than  length  of  normal 
normocyte.    Nucleus  round,  of  same  color  or  slightly  purple,  but  larger 
and  with  more  scattered  chromatin  than  nucleus  of  normal  normocyte. 
Cytoplasm  greenish-blue  and  glassy.    Frequently  with  clear  zone  about 
nucleus. 

3.  Megaloblast  (d)  :  Same,  except  diameter  equal  to  or  greater  than 
length  of  normal  normocyte. 

4.  Mitotic  Cells  (e)  :  All  stages,  from  monaster  to  complete  division 
of  nucleus,     (a)  Eound  or  elliptical,  diameter  about  length  of  normal 
normocyte.    Dense,  deep  blue  chromosomes,  massed  in  center  of  cell. 
Cytoplasm  greenish-blue  and  glassy,   (b)   Same,  with  two  masses  of 
chromosomes  in  opposite  extremes  of  cell,  (c)  Same  (at  times  with  a 
slight  constriction  in  the  middle  of  the  cell)  with  irregular,  dense,  deep 
blue  or  slightly  purple  chromatin  masses  in  place  of  individual  chromo- 
somes,  (d)   Same,  with  two  nuclei,  similar  in  appearance  to  those  of 
normoblast.  (e)   Same  as  normal  normocyte  with  two  nuclei,  similar  in 
appearance  to  those  of  normoblast,  but  only  slightly  larger  than  nucleus 
of  normal  normocyte.     (a),  (b),  (c)  and  (d)  may  show  polychroma- 
tophilic  cytoplasm. 

Blood  Platelets  (/). 

1.  Same  as  normal,  except  that  cell  and  nucleus  are  both  larger. 

2.  Larger  than  normal  with  two  nuclei. 

Leucocytes. 

1.  Polymorphonuclear  leucocyte  with  eosinophilic  rods  (g) :  Same 
as  in  normal  blood,  at  times  possibly  a  little  smaller. 

2.  Polymorphonuclear  leucocyte   with  eosinophilic  granules    (h) : 
Same  as  in  normal  blood,  at  times  possibly  a  little  smaller. 

3.  Lymphocyte  (i)  :  Same  as  in  normal  blood. 

4.  Large  mononuclear  cell :  (a)  As  described  in  normal  blood,  with 
a  little  less  cytoplasm,   (b)   Same  size  to  one  half  times  larger  than  (a), 
with  both  nucleus  and  cytoplasm  paler  (/).     (a)  and  (b)  cannot  be 
separated  absolutely.    Every  gradation,     (c)  Mitoses  (fc) :  All  stages, 
from  monaster  to  complete  separation  of  nucleus,     (a')   Elliptical, 
diameter  about  one  and  a  half  length  of  normal  normocyte.     Dense, 
purple  chromosomes  centrally  massed.     Cytoplasm  pale  bluish-gray, 


24:  Harry  C.  Schmeisser. 

granular,  (b')  Same,  with  two  masses  of  chromosomes  in  opposite  ex- 
tremes of  the  cell,  (c')  Same,  with  two  purple  nuclei,  (d')  Same,  with 
three  purple  nuclei. 

5.  Mast  Cell  (Z)  :  As  described  in  normal  blood. 

6.  Mononuclear  myelocyte  with  eosinophilic  granules   (ra)  :  Eound 
or  slightly  elliptical,  diameter  about  length  of  normal  normocyte  or 
longer.     Nucleus,  oval,  pale  blue  with  dense  chromatin,  eccentric. 
Cytoplasm  colorless  with  small  and  large,  bright  red  granules,  some 
scattered  over  granules. 

Cytoplasmatic  Masses  without  Nuclei  (n)  :  Eound  or  slightly  oval; 
diameter  varies,  usually  about  width  of  normal  normocyte.  No  nucleus. 
Cytoplasm  grayish-blue,  sometimes  with  vacuoles. 

This,  then,  is  the  blood  picture  common  to  all  the  leukaemic  cases. 
The  order  of  predominance  of  the  white  cells  is  typical  of  leukaemia, 
differing  from  the  normal,  but  agreeing  with  that  of  the  spontaneous 
case.  The  large  mononuclear  is  present,  by  far,  in  greatest  numbers. 
The  other  cells  of  the  normal  blood  are  decreased.  The  polymorphonu- 
clear  with  eosinophilic  granules  and  the  mast  cell  are  very  scarce.  The 
mononuclear  myelocyte  with  eosinophilic  granules,  although  not  as 
common  as  in  the  spontaneous  case,  can  usually  be  demonstrated  in 
every  leuksemic  animal. 

The  platelets  are  greatly  increased  in  number. 

Differential  Count,  300  Cells. 

Per  cent. 

Polymorphonuclear  with  eosinophilic  rods 6 

Polymorphonuclear  with  eosinophilic  granules 0 

Lymphocyte    4 

Large  mononuclear  cell 86 

Mast    cell 1 

Mononuclear  myelocyte  with  eosinophilic  granules ...  1 

Unclassified  cells 2 

100 

AUTOPSY    FINDINGS. 

The  weight  of  the  animal  in  every  case  was  far  below  its  weight  before 
injection.*  Two  lowest  weights,  at  autopsy,  were  675  and  897  gm. 

External  Appearance. — The  jaundice  was  found  at  times  to  involve 
the  skin  of  the  entire  body.f  The  conjunctivas  and  buccal  mucous  mem- 

*  Animals  which  remained  negative  invariably  gained  in  weight, 
f  Probably  this  was  more  frequent  but  not  recognized,  except  when  very 
grave,  because  of  the  normal  yellow  tint  of  the  skin. 


Leukcemia  of  the  Fowl.  25 

branes  were  always  very  pale.  The  eyes,  nose  and  mouth  were  never 
involved.  There  was  extreme  emaciation,  and  great  scarcity  or  entire 
absence  of  subcutaneous  fat.  Muscular  atrophy  was  usually  marked,  at 
times  practically  only  the  skeleton  remained  (Fig.  5). 

Cervical  Lymph-glands. — Macroscopically,  these  were  usually  unin- 
volved.  In  two  cases  they  were  definitely  enlarged  (Fig.  3,  a  and  b),  in 
the  one  very  much  so,  measuring  1.5  x  8  x  4  cm.  and  2  x  1  x  .5  cm., 
respectively.  They  appeared  uniformly  gray.  The  lobules  of  the  par- 
enchyma were  enlarged  and  the  interlobular  fat  had  disappeared.  In  a 
third  case,  they  were  of  normal  size  and  appearance,  but  showed  several 
gray  nodules,  1  mm.  in  diameter.  Microscopically,  those  glands  which 
appeared  normal  in  gross  were  usually  free  from  myeloid  infiltration, 
although  their  blood-vessels  contained  leuksemic  blood.  The  diffusely 
enlarged  glands  showed  a  marked  swelling  of  their  parenchyma,  with 
complete  atrophy  of  the  interlobular  fat.  Myeloid  cells,  both  the  large 
mononuclear  and  the  mononuclear  myelocyte  with  eosinophilic  granules, 
were  scattered  through  the  lobules.  Foci,  some  composed  entirely  of 
the  first,  and  others  exclusively  of  the  second,  were  localized  principally 
in  the  interlobular  connective  tissue.  They  were  rich  in  mitotic  figures. 
The  gray  nodules  seen  in  gross  proved  to  be  masses  of  proliferating 
myeloid  cells.  All  the  blood-vessels  were  filled  with  the  characteristic 
blood. 

Thyroids  and  Parathyroids. — These  were  grossly  and  microscopically 
uninvolved,  with  the  exception  of  the  blood-vessels,  which  were  filled 
with  leukaemic  blood. 

Peritoneal  Cavity. — In  every  case  the  omental  fat  was  greatly  de- 
creased. At  best,  it  was  present  only  in  moderate  amount.  As  a  rule 
it  was  replaced  by  a  thin  yellow  membrane.  Ascites  occurred  in  six  out 
of  13  cases,  at  times  in  sufficient  quantity  to  distend  the  abdomen.  It 
was  always  associated  with  a  sero-fibrinous  mass,  which  covered  not  only 
the  liver  and  most  of  the  other  abdominal  viscera,  but  also  spread  over 
the  outer  surface  of  the  pericardium. 

With  enlargement  of  the  liver,  the  lower  margins  of  its  two  lobes 
change  their  position  in  relation  to  the  tip  of  the  xiphoid.  They 
descend  to  this  landmark  and  frequently  extend  far  beyond.  With  the 
exception  of  Nos.  31  and  70,  every  animal  of  the  13  had  an  enlarged  liver 
(Table  1) .  The  margins  of  the  right  and  left  lobes  of  the  smallest  of  the 
enlarged  livers  were,  respectively,  1  and  3  cm.  above  the  xiphoid,  while 
the  margins  of  the  largest  liver  extended  3.5  and  3  cm.,  respectively, 


26  Harry  C.  Schmeisser. 

below  it.  In  fact,  the  latter  organ  in  situ  (Fig.  5)  was  so  enormous  that 
it  filled  the  entire  peritoneal  cavity  and  was  the  only  viscus  visible  on 
entering  the  abdomen. 

Liver. — As  mentioned,  the  liver  was  greatly  enlarged  in  11  cases 
(Table  1),  frequently  enormous  (Fig.  5).  In  the  smallest  of  these 
the  right  lobe  measured  9  x  4.5  x  3.8  cm. ;  the  left  lobe,  7  x  5  x  3.8  cm. ; 
in  the  largest,  right  lobe  13.5  x  4.5  x  4  cm. ;  left  lobe  12.5  x  4  x  3.5  cm. 
On  comparing  them  with  the  normal,  these  dimensions  are  not  very  con- 
vincing, with  the  exception  of  the  length  of  the  lobes.  As  the  organ 
enlarges,  it  becomes  distorted,  because  the  limited  cross-diameter  of  the 
peritoneal  cavity  prevents  its  expansion  in  this  direction  and  forces  the 
lobes  to  follow  the  costal  framework,  posteriorly.  The  long  diameters 
of  the  lobes  are  more  reliable,  because  the  organ  can  enlarge  freely  in 
this  direction. 

The  weight  of  the  liver  is  a  more  accurate  indication  of  its  size, 
especially  when  expressed  in  per  cent  of  body  weight,  i.  e.,  the  number  of 
grams  of  weight  of  organ  per  100  gm.  of  weight  of  the  animal  at  death. 
Thus,  the  weights  were  found  to  range  from  80-265  gm,  i.  e.,  they  were 
over  five  times  the  normal  or  6.2-10.3  per  cent  of  body-weight,  an 
increase  of  3.6+  times  the  normal  (Table  1). 

The  external  appearance  of  the  liver  may  not  differ  much  from  the 
normal,  but  usually  it  is  very  characteristic  ( Fig.  5 ) .  It  may  appear 
diffusely  gray,  due  to  very  closely  packed  subcapsular  spots,  pin-point  to 
2  mm.  in  diameter.  These  are  usually  more  scattered  and  translucent, 
at  times  slightly  yellow  and  opaque.  They  may  fuse  to  form  larger 
areas  with  a  diameter  of  0.5-1  cm.,  or  they  may  be  arranged  in  a  delicate 
gray  network.  In  addition,  numerous  gray  or  slightly  yellow  nodules, 
ranging  from  2-0.5  cm.  in  diameter  are  often  present.  The  whole  gives 
the  surface  an  extremely  mottled  appearance.  Lobulation  at  times  is 
visible,  usually  indistinct.  The  liver  may  be  slightly  firm  or  friable. 
The  sectioned  surface  appears  very  similar  to  the  external  surface.  Dots 
and  lines  often  form  gray  borders  along  the  blood-vessels.  The  latter 
also  occupy  the  centers  of  some  of  the  larger,  circumscribed,  gray  areas. 
The  perivascular  connective  tissue  in  rare  instances  is  bile-stained. 
Microscopically,  there  is  usually  a  diffuse  infiltration  of  myeloid  cells. 
They  are  closely  packed  within  and  without  the  intralobular  capillaries. 
The  liver  trabeculae  show  fatty  degeneration  and  atrophy.  The  large 
mononuclear,  rich  in  mitotic  figures,  is  by  far  the  predominating  cell. 


Leukcemia  of  the  Fowl.  27 

The  mononuclear  myelocyte  with  eosinophilic  granules  is  very  scarce. 
Scattered  through  the  section  are  also  foci  of  large  mononuclears,  or  of 
mononuclear  myelocytes  with  eosinophilic  granules.  Some  contain  both 
types  of  cells.  They  abound  in  mitotic  figures.  The  liver  cells  in  these 
foci  have  entirely  disappeared.  The  small,  gray  nodules  consist  of  cir- 
cumscribed masses  of  myeloid  tissue,  usually  occupying  the  periportal 
spaces  and  composed  of  a  central  portion  of  large  mononuclears  sur- 
rounded by  the  mononuclear  myelocyte  with  eosinophilic  granules.  In 
the  blood-vessels  and  capillaries,  the  large  mononuclear,  at  times,  seems 
to  greatly  exceed  the  red  blood  cell  in  numbers. 

Spleen. — Except  in  Nos.  31  and  70,  the  spleen  in  every  case  was  en- 
larged (Table  1)  ;  usually  very  much  (Fig.  6).  The  dimensions,  in 
contrast  to  those  of  the  liver,  are  of  definite  comparative  value.  The 
smallest  of  the  enlarged  organs  measured  3  x  2  x  1.7  cm.,  the  largest 
4  x  3  x  2.3  cm.,  the  latter  being  just  twice  the  normal  in  every 
dimension. 

The  weights  were  strikingly  increased.  The  lowest  was  6  gin.,  the 
highest,  18  gm.,  i.  e.  18  times  the  normal,  or  .6-1.6  per  cent  of  the  body 
weight,  i.  e.,  32  times  the  normal. 

The  surface  of  the  spleen  may  look  normal,  be  reddish  brown  and 
show  beneath  its  capsule  pin-point,  gray  Malpighian  bodies.  More  fre- 
quently one  sees  scattered,  gray  or  slightly  yellow  spots  and  nodules 
(Fig.  6),  the  first  from  1-3  mm.,  and  the  largest  of  the  second  from 
0.5-1  cm.  in  diameter.  Again,  the  organ  appears  just  diffusely  gray.  A 
section  (Fig.  6)  appears  usually  the  same  as  the  surface.  When  difj 
fusely  gray,  the  pulp  is  somewhat  granular  and  bulges.  Microscopically, 
the  entire  pulp  may  be  diffusely  infiltrated  with  the  large  mononuclear 
cell,  separating  and  compressing  the  Malpighian  bodies.  In  addition, 
circumscribed,  closely  packed  masses  of  pure  large  mononuclears  or 
mononuclear  myelocytes  with  eosinophilic  granules  are  scattered 
through  the  section.  Again,  the  myelosis  may  be  present  only  in 
foci,  with  practically  no  disturbance  of  the  normal  splenic  structure. 
Mitoses  are  abundant  wherever  the  large  mononuclear  occurs.  The  con- 
tents of  the  blood-vessels  are  the  same  as  in  the  liver. 

Heart. — As  mentioned  above,  the  external  surface  of  the  pericardium 
is  frequently  covered  with  a  serofibrinous  mass.  The  heart  itself  may  be 
somewhat  enlarged,  otherwise  it  appears  normal  (Fig.  5).  Micro- 
scopically also  there  is  little  to  be  seen  besides  a  great  excess  of  the  large 


28  Harry  C.  Schmeisser. 

mononuclear  in  the  intramuscular  capillaries,  with  an  occasional  small 
extravascular  focus  of  infiltration,  consisting  of  the  same  cell. 

Lungs. — These  are  seldom  involved.  In  two  cases  they  were  cedemat- 
ous.  In  one,  the  tubular  walls  were  wide  and  gray,  occluding  the 
lumina.  On  section,  the  latter  case  presented  a  similar  but  more  marked 
picture.  Microscopically  the  intertubular  blood-vessels,  their  branches 
which  extend  into  the  capillary  bed,  and  the  capillaries  themselves,  are 
always  filled  with  leukaemic  blood.  At  times  they  are  greatly  distended. 
The  white  cells  are  always  increased  in  number,  and  sometimes  the 
blood  seems  to  consist  solely  of  closely  packed,  large  mononuclears. 
Mitoses  are  everywhere  abundant.  Very  rarely,  a  few  mononuclear 
myelocytes  with  eosinophilic  granules  or  large  mononuclears  are  gath- 
ered in  small  masses  in  the  intertubular  connective  tissue. 

Gastro-intestinal  Tract,  Pancreas  and  Adrenals. — These  in  gross 
showed  nothing  of  interest.  No  mesenteric  lymph-glands  were  demon- 
strated. The  pancreas,  microscopically  in  no  case  showed  any  infiltra- 
tion of  its  parenchyma  proper,  but  in  several  there  were  numerous  nests 
of  myeloid  cells  in  the  interlobar  fat  tissue,  usually  surrounding  one  or 
more  capillaries,  and  composed  of  the  large  mononuclear,  eosinophilic 
myelocytes,  both  mononuclear  and  polymorphonuclear.  Mitoses  of  both 
the  mononuclears  were  frequent.  The  blood-vessels  in  the  parenchyma 
and  fatty  tissue  contained,  as  usual,  the  predominating  large  mononu- 
clear. 

The  adrenals  also  reveal  interesting  findings  histologically.  It  is 
quite  common  for  the  intertrabecular  capillaries  to  be  enormously  dis- 
tended with  the  characteristic  leukaemic  blood  and  for  the  myeloid  cells 
to  have  infiltrated  between  the  capillary  wall  and  parenchymatous  cells. 
These  nests  contain  mostly  the  large  mononuclear,  but  now  and  again 
they  seem  to  be  very  rich  in  lymphocytes.  The  parenchyma  has  suffered 
greatly;  its  nuclei  stain  poorly  and  frequently  its  cells  show  disinte- 
gration. 

Kidneys. — Of  the  13  cases,  the  kidneys  of  five  were  enlarged.  The 
smallest  measured  7  x  1.5  x  1.2  cm.,  the  largest  7.2  x  2.2  x  1.4  cm.  The 
weight  of  both  kidneys  ranged  from  12-26  gm.,  or  0.8-1.4  per  cent  of 
the  body-weight.  In  one  case  the  kidneys  were  extremely  oedematous 
and  weighed  32  gm.  or  2  per  cent  of  the  body-weight. 

The  surface  and  section  of  the  kidney  may  appear  entirely  normal, 
but  usually  one  can  see,  below  its  capsule,  scattered,  gray  pin-point  dots, 


Leukaemia  of  the  Fowl.  29 

delicate  lines,  or  even  one  or  two  nodules,  the  largest  0.5  cm.  in  diameter. 
Again,  they  may  appear  diffusely  gray.  In  the  one  case,  they  were  large, 
succulent  and  translucent,  due  to  oedema.  Microscopically,  the  kidneys 
always  show  more  or  less  distension  of  their  blood-vessels  and  inter- 
tubular  capillaries  with  the  characteristic  leukaemic  blood,  in  which 
white  blood  cells,  at  times,  seem  even  to  exceed  the  normocytes,  and  in 
which  the  large  mononuclear  predominates.  When  capillary  distension 
is  moderate,  the  tubules  appear  normal ;  but  at  times  they  are  so  enor- 
mously over-filled  as  to  cause  extreme  atrophy  and  degeneration  of  the 
tubular  epithelium,  resulting  frequently  in  circumscribed  areas  devoid 
of  any  parenchyma.  These  areas  tend  to  form  a  kind  of  zone  about  the 
larger  blood-vessels.  The  glomeruli  are  surprisingly  free.  The  walls 
and  perivascular  tissue  of  some  of  the  vessels  are  infiltrated  with 
actively  generating  myeloid  cells,  especially  the  large  mononuclear. 

Bone-marrow. — This  is  always  involved,  usually  more  or  less  char- 
acteristically, being  increased  in  amount,  moderately  soft  and  red,  mot- 
tled with  countless  gray  dots  to  slightly  larger  areas,  or  it  may  be  dif- 
fusely gray.  In  either  case  the  fat  is  absent  entirely  and  red  blood 
cells  are  very  scarce.  The  marrow  may  be  involved  as  a  whole  or  only 
in  part.  Now  and  again  it  has  been  converted  into  a  uniformly  gray, 
dry  and  slightly  firm  column,  which  bulges  from  the  marrow  cavity. 
In  such  cases  it  is  obviously  very  rich  in  white  cells,  poor  in  red  cells  and 
fat.  Microscopically,  the  normal  structure  of  the  marrow  is  greatly 
changed.  The  fatty  tissue  has  completely  disappeared  and  the  marrow 
cells  are  closely  packed  in  a  solid  mass,  in  which  the  normocyte  is 
rather  inconspicuous.  The  arteries  in  the  center  of  the  marrow  are 
poor  in  blood.  One  or  two  contain  a  few  normocytes  and  large  mononu- 
clears.  The  description  of  the  red  and  white  cells,  which  are  present 
agrees  with  that  given  under  normal  marrow.  Possibly  the  large 
mononuclear  is  more  commonly  polygonal,  due  to  pressure.  Mitoses  of 
both  the  large  mononuclear  and  the  erythrocytes  are  common  especially 
the  first.  The  order  of  predominance  has  changed  from  the  normal. 
The  large  mononuclear  myelocyte  is  present  by  far  in  greatest  numbers ; 
the  normoblast,  megaloblast  and  mononuclear  myelocyte  with  eosino- 
philic  granules  follow  in  about  equal  numbers;  the  normocyte  comes 
last.  Both  types  of  polymorphonuclear  cells,  as  well  as  the  lymphocyte, 
mast  cells  and  platelets  were  not  seen  at  all.  Mitoses  of  the  mononu- 
clear myelocyte  with  eosinophilic  granules  were  not  demonstrated. 


30 


Harry  C.  Schmeisser. 


TABLE  1— EXPERIMENTAL  LEUKAEMIA. 

WEIGHTS,  IN  GRAMS  OF  BODY,  OBGANS  AND  RELATION  OF  OBGANS  TO  BODY 

AT  AUTOPSY. 


Animal 
No. 

Body. 

Liver. 

Liver  to 
body  %. 

Spleen. 

Spleen  to 
body  %. 

Kidneys. 

Kidneys  to 
body  %. 

Normal 

1760 

50 

2.8 

1 

0.05 

12 

0.7 

1 

1515 

117 

7.7 

11 

0.7 

20 

1.3 

6 

1200 

124 

10.3 

15 

1.2 

10 

0.8 

12 

i 

95 

15 

.... 

.... 

14 

1573 

125 

'7!9 

18 

'i!i 

32  * 

'2!o 

15 

1660 

116 

6.9 

10 

0.6 

20 

1.2 

24s 

28 

897 

85 

9.6 

'<j 

'6!f 

30 

1410 

107 

7.6 

17 

0.6 

31 

675 

20 

2.9 

3 

.4 

5 

'6'.  7 

53 

.... 

265 

12 

57 

1070 

91 

8.5 

18 

'i!e 

15 

1A 

70  « 

65 

4 

.... 

26 

103 

1282 

80 

6.2 

8 

0.6 

12 

0.9 

1  Not  weighed. 
*  Very  cedematous. 

3  Whole  animal  kept  as  a  museum  specimen.    Illustrated,  Fig.  5. 

4  Spontaneously  cured.  Not  leukxmic  at  death. 


SUMMARY. 

In  summarizing  the  essential  points  deduced  by  the  simple  trans- 
mission of  leukaemia  by  the  injection  of  an  organic  emulsion,  we  shall 
consider : 

1.  Clinical  History. — After  an  incubation  period,  usually  from  five  to 
six  weeks,  the  fowl  suddenly  becomes  pale,  jaundiced,  emaciates  rapidly, 
loses  weight  and  shows  signs  of  extreme  weakness,  followed  almost  with- 
out exception  by  death  in  one  to  two  weeks. 

2.  Blood. — (a)  The  total  number  of  white  blood  cells  is  greatly  in- 
creased, resulting  in  a  proportion  of  one  white  to  three  red  blood  cells. 
The  differential  count  shows  a  marked  increase  and  predominance  of 
the  large  mononuclear  over  the  other  white  cells  of  the  normal  blood, 
which  have  decreased.    The  mononuclear  myelocyte  with  eosinophilic 
granules  is  present  in  more  or  less  numbers  in  practically  every  case. 
Besides  the  normal-appearing  large  mononuclear,  one  sees  many  larger, 
pale  forms.    In  these  cells,  mitoses,  in  all  stages,  typical  and  atypical, 
are  common,     (b)  The  total  number  of  red  blood  cells  is  correspond- 
ingly decreased,  with  a  marked  fall  in  the  haemoglobin.    They  present 


Leukaemia  of  the  Fowl.  31 

variations  in  size,  shape  and  staining,  associated  with  swelling  of  the 
nucleus.  Normoblasts,  megaloblasts,  with  mitoses  in  all  stages  make 
their  appearance,  (c)  There  is  an  increase  in  the  number  of  the  blood 
platelets,  associated  with  an  increase  both  in  the  size  of  the  cell  and  the 
nucleus.  The  cells  frequently  contain  more  than  one  nucleus,  (d)  The 
blood  loses  its  power  of  clotting. 

3.  Organic  Findings. —  (a)  There  is  a  diffuse,  focal,  less  frequently 
a  nodular  infiltration  of  marrow  cells,  in  which  the  large  mononuclear 
and  mononuclear  myelocyte  with  eosinophilic  granules  predominate. 
The  foci  may  be  limited  to  the  large  mononuclear  or  granular  eosino- 
philic myelocytes,  commonly  the  mononuclear,  or  may  be  composed  of 
both  types.  Extensive  mitoses  testify  to  active  proliferation.  This 
myelosis  affects  most  particularly  the  liver,  spleen,  kidneys  and  bone- 
marrow,  causing  a  great  increase  in  the  size  of  the  first  three  organs. 
Rarely,  the  cervical  lymph-glands  are  also  very  much  enlarged.  Most 
of  the  remaining  organs  and  neighboring  tissues  may  contain  infiltra- 
tions but  not  so  extensive,  (b)  The  relative  proportion  of  white  to  red 
blood  cells  is  greatly  increased  in  the  blood-vessels.  The  same  cells  pre- 
dominate as  in  the  infiltrations,  (c)  There  are  atrophic  and  degenera- 
tive changes  of  the  parenchyma,  general  atrophy  of  the  adipose  tissue, 
ascites  etc. 

CONCLUSION. 

The  injection  of  an  organic  emulsion  causes  a  picture  of  myeloid 
leukaemia  in  every  respect  similar  to  that  of  spontaneous  leukaemia  as  it 
occurs  in  the  fowl. 

The  chemical  picture  and  changes  produced  in  the  blood  and  organs 
are  analogous  to  those  which  occur  in  human  leukaemia. 

V.  CONCLUSION. 

1.  The  spontaneous  occurrence  of  myeloid  leukaemia  of  the  fowl  is 
confirmed. 

2.  Myeloid  leukaemia  in  the  fowl  is  transmissible  by  the  intravenous 
or  intraperitoneal  injection  of  an  organic  emulsion.    The  latter  is  in 
confirmation  of  the  work  by  Ellermann  and  Bang  who,  as  I  have  stated, 
were  the  first  to  successfully  transmit  the  disease.    They  were  followed 
by  Hirschfeld  and  Jacoby,  whose  successful  transmissions,  however, 
seem  to  be  limited  to  a  strain,  which  had  its  origin  in  a  fowl  presented 
to  them  by  Ellermann  and  Bang.    Burckhardt  likewise  transmitted  the 

3 


32  Harry  C.  Schmeisser. 

disease,  but  here  again  the  stock  animal  came  from  Hirschfeld  and 
Jacoby,  and  therefore  indirectly  from  Ellermann  and  Bang. 

The  above  reported  transmission  is  of  special  interest,  because  it 
originated  from  an  animal  entirely  independent  and  far  remote  from 
those  of  the  previous  investigators. 

LITERATURE  OF  LEUKEMIA  IN  THE  FOWL. 

1.  MOORE,  V.  A.:   Infectious  Leukaemia  in  Fowls — A  Bacterial  Dis- 

ease Frequently  Mistaken  for  Fowl  Cholera.  Twelfth  and 
Thirteenth  Annual  Eeports,  Bureau  of  Animal  Industry, 
U.  S.,  1895-1896,  185-205. 

2.  BUTTERFIELD,  E.  E. :    Aleukaemic  Lymphadenoid  Tumors  of  the 

Hen.    Folia  haemat.,  1905,  II,  649-657. 

3.  WARTHIN,  A.  S. :  Leukaemia  of  the  Common  Fowl.    Jour.  Infect. 

Dis.,  1907,  IV,  369-381. 

4.  KON,  J. :   Ueber  Leukamie  beim  Huhn.    Virchows  Arch,  f .  path. 

Anat.,  1907,  CXC,  338-349. 

5.  SOSHESTRENSKI,  N.  A.:     (Leukaemia  of  the  Chicken.)     Uchen. 

zapiski  Kazan.    Vet.  Inst.,  1908,  XXV,  215-222. 

6.  ELLERMANN,  V.,  and- BANG,  0.:     Experimentelle  Leukamie  bei 

Huhnern.    Vorlaufige  Mitteilung.     Centralbl.  f.  Bakteriol., 

1908,  Theil  1,  Orig.,  XLVI,  4-5. 

7.  Experimentelle   Leukamie   bei   Huhnern.      Centralbl.   f. 

Bakteriol.,  1908,  Theil  1,  Orig.,  XLVI,  595-609. 

8.  Experimentelle  Leukamie  bei  Huhnern.    Verhandl.  d.  d. 

path.  Gesellsch.,  1908,  XII,  224-225. 

9.  -  (Experimental  Leukaemia  in  Fowls.)      Overs,   v.   d.  k. 

Danske  Vidensk.   Selsk.    Torh.,  Kbenk.,  1908,  65-94;  ibid., 

1909,  p.  261. 

10.  -          -  Experimentelle  Leukamie  bei  Hiihnern.    Ztschr.  f.  Hyg. 

u.  Infektionskrankh.,  1909,  LXIII,  231-272. 

11.  SCHRIDDE:     Gibt  es  eine  infektiose  Aetiologie  der  Leukamie? 

Deutsche  med.  Wchnschr.,  1909,  XXXV,  280. 

12.  HIRSCHFELD,  H.,  and  JACOBY,  M. :    Zur  Kenntnis  der  iibertrag- 

baren  Hiihnerleukamie.  Berl.  klin.  Wchnschr.,  1909,  XLVI, 
159-160. 

13. Uebertragbare  Hiihnerleukamie.     Berl.  klin.  Wchnschr., 

1909,  XLVI,  314. 


Leukcemia  of  the  Fowl.  33 

14.  HIRSCHFELD,  H.,  and  JACOBY,  M.:    Uebertragungsversuche  mit 

Huhnerleukamie.     Ztschr.  f.  klin.  Med.,  1910,  LXIX,  107- 
120. 

15.  BUECKHARDT,  J.  L. :   (Bei  der  82.    Versammhmg  Deutscher  Natur- 

forscher  und  Aerzte  zu  Konigsberg.)    Ztschr.  f.  Immunitats- 
forsch.  u.  exper.  Therap.,  1910,  Theil  2,  810-811. 

16.  Ueber  das  Blutbild  bei  Hiihnertuberkulose  und  dessen 

Beziehungen  zur  sogenannten  Huhnerleukamie,  nebst  Bemer- 
kungen  iiber  das  normale  Hiihnerblut.  Ztschr.  f .  Immunitats- 
forsch.  u.  exper.  Therap.  1912,  XIV,  544-604. 

17.  HIRSCHFELD,  H.,  and  JACOBY,  M. :  Uebertragbare  Huhnerleukamie 

und  ihre  Unabhangigkeit  von  der  Hiihnertuberculose.  Ztschr. 
f.  klin.  Med.,  1912,  LXXV,  501-505. 

18.  ELLERMANN,  V:     Unders0geler  over  H0nseleukaemiens  Virus. 

Urgesk.  f.  Laeger,  1913,  LXXV,  1685-1691. 

19.  Untersuchungen  iiber   das   Virus    der  Hiihnerleukamie. 

Ztschr.  f.  klin.  Med.,  1914,  LXXIX,  43-48. 

EXPLANATION  OF  FIGURES. 

FIG.  1. — Normal  blood  of  the  fowl.  Wilson's  stain.  Zeiss  objective  1/12, 
eye-piece  No.  3.  Composite  picture,  (a)  Normocytes.  (b)  Blood  plate- 
lets, (c)  Polymorphonuclear  leucocyte  with  eosinophilic  rods,  (d)  Poly- 
morphonuclear  leucocyte  with  eosinophilic  granules,  (e,  e')  Lymphocytes 
(small  and  large).  (/)  Large  mononuclear  cell,  (g)  Mast  cell. 

FIG.  2. — Leukaemic  blood  of  the  fowl.  Wilson's  stain.  Zeiss  objective 
1/12,  eye-piece  No.  3.  Composite  picture,  (a)  Normal  normocytes.  (6) 
Normocytes  showing  anisocytosis,  poikilocytosis,  polychromatophilia, 
with  swelling  of  nucleus  and  separation  of  its  chromatin.  (c)  Normoblast. 
(d)  Megaloblast.  (e)  Mitoses  of  erythrocytes ;  all  stages  from  monaster 
to  complete  division  of  nucleus.  (/)  Blood  platelets;  both  cell  and  nucleus 
increased  in  size;  increase  in  size  with  two  nuclei,  (g)  Polymorphonu- 
clear leucocyte  with  eosinophilic  rods,  (h)  Polymorphonuclear  leucocyte 
with  eosinophilic  granules,  (i)  Lymphocyte.  (;')  Large  mononuclear 
cell;  same  size  and  larger  than  normal  with  both  nucleus  and  cytoplasm 
paler,  (fc)  Mitoses  of  large  mononuclear  cell;  all  stages,  from  monaster 
to  complete  separation  of  nucleus.  (I)  Mast  cell,  (m)  Mononuclear 
myelocyte  with  eosinophilic' granules,  (n)  Cytoplasmatic  masses  without 
nuclei. 

FIG.  3. — Cervical  lymph-glands  of  the  fowl ;  normal  and  leukaemic.  Actual 
size  and  X  2.  Note  the  great  increase  in  size;  replacement  of  fat  by  the 
greatly  swollen  parenchymatous  lobules. 

FIG.  4. — Normal  fowl  with  organs  in  situ.  Weight,  1750  gm.  Note  the 
well-nourished  condition  of  the  body;  the  abundance  of  fat,  subcutaneously, 


34  Harry  C.  Schmeisser. 

in  the  neck,  and  in  the  omentum;  the  large  muscles;  size  of  heart  and 
liver. 

FIG.  5. — Leukaemic  fowl  with  organs  in  situ.  Weight,  1350  gm.  Note 
great  emaciation  of  body;  almost  entire  absence  of  fat;  atrophy  of  muscles; 
large  heart;  enormous  liver  with  the  characteristic  myeloid  infiltrations. 

FIG.  6. — Spleen  of  the  fowl;  normal  and  leukaemic,  actual  size;  surface 
and  section.  Note  the  enormous  increase  in  size;  in  upper  half  of  surface, 
circumscribed  areas  of  myeloid  infiltration;  the  swollen  pulp  and  infiltra 
tions  on  section. 


DESCRIPTION  OF  PLATE   I. 

FIG.  1. — Normal  blood  of  the  fowl.  Wilson's  stain.  Zeiss  objective  1/12, 
eye-piece  No.  3.  Composite  picture,  (a)  Normocytes.  (6)  Blood  platelets. 

(c)  Polymorphonuclear  leucocyte  with  eosinophilic  rods,     (d)   Polymor- 
phonuclear    leucocyte    with    eosinophilic    granules,     (e.e)    Lymphocytes 
(small  and  large).     (/)  Large  mononuclear  cell,     (g)  Mast  cell. ^-^xv^-o-/? 

FIG.  2. — Leukaemic  blood  of  the  fowl.  Wilson's  stain.  Zeiss  objective 
1/12,  eye-piece  No.  3.  Composite  picture,  (a)  Normal  normocytes.  (&) 
Normocytes  showing  anisocytosis,  poikilocytosis,  polychromatophilia,  with 
swelling  of  nucleus  and  separation  of  its  chromatin.  (c)  Normoblast. 

(d)  Megaloblast.     (e)  Mitoses  of  erythrocytes,  all  stages  from  monaster 
to  complete  division  of  nucleus.     (/)  Blood  platelets;  both  cell  and  nucleus 
increased  in  size;  increase  in  size  with  two  nuclei,     (g)   Polymorphonu- 
clear leucocyte  with  eosinophilic  rods.     (7i)  Polymorphonuclear  leucocyte 
with   eosinophilic   granules,      (i)  Lymphocyte.      (;')  Large    mononuclear 
cell;  same  size  and  larger  than  normal  with  both  nucleus  and  cytoplasm 
paler,     (fc)  Mitoses  of  large  mononuclear  cell;  all  stages,  from  monaster 
to   complete   separation    of   nucleus.      (I)  Mast   cell,      (m)  Mononuclear 
myelocyte  with  eosinophilic  granules.     (»)  Cytoplasmatic  masses  without 
nuclei. 


THE  JOHNS   HOPKINS  HOSPITAL  REPORTS. 


PLATE    I. 


••   9 

b" 

^ 


A    ^ 

b 


a 


e 


e 


• 


g     • 


FIG.  1. 


*«/ 

A    ( 

I** 


*    ®     " 


^- 


& 


FIG.  2. 


Dorothea  Pennington  fee. 


THE  JOHNS  HOPKINS  HOSPITAL   REPORTS. 


PLATE   II. 


Actual  size. 


Leu 


FIG.  3.— Cervical  lymphglands  of  the  fowl;  nor- 
mal and  leukaemic.  Actual  size  and  X  2.  Note 
the  great  increase  in  size;  replacement  of  fat  by 
the  greatly  swollen  parenchymatous  lobules. 


Normal  spleen 

actual  size 


Surface 


• 

Section 


Leukaemic   spleen 

actual  size 


Surface 


Sect 


ion 


FIG.  6. — Spleen  of  the  fowl;  normal  and  leukaemic,  actual 
size;  surface  and  section.  Note  the  enormous  increase  in 
size;  in  upper  half  of  surface  circumscribed  areas  of  myeloid 
infiltration;  the  swollen  pulp  and  infiltrations  on  section. 


THE  JOHNS  HOPKINS   HOSPITAL   REPORTS. 


PLATE 


mamm 


FIG.  4. — Normal  fowl  with  organs  in  situ.  Weight,  1750  gm.  Note  the 
well-nourished  condition  of  the  body;  the  abundance  of  fat,  subcutaneously, 
in  the  neck,  and  in  the  omentum;  the  large  muscles;  size  of  heart  and  liver. 


THE   JOHNS   HOPKINS   HOSPITAL   REPORTS. 


PLATE    IV. 


FIG.  5. — Leukaemic  fowl  with  organs  in  situ.  Weight,  1350  gm.  Note  great 
emaciation  of  body;  almost  entire  absence  of  fat;  atrophy  of  muscles;  large 
heart;  and  enormous  liver  with  the  characteristic  myeloid  infiltrations. 


SEPARATE  MONOGRAPHS  REPRINTED  FROM  THE  JOHNS 
HOPKINS  HOSPITAL  REPORTS. 

Studies  In  Dermatology.  By  T.  C.  GTJLCHBIST,  M.  D.,  and  EMMET  RIXFOBD, 
M.  D.  164  pages  and  41  plates.  Price,  in  paper,  $3.00. 

The  Malarial  Fevers  of  Baltimore.  By  W.  S.  THAYEB,  M.  D.,  and  J.  HEWET- 
soif ,  M.  D.  And  A  Study  of  some  Fatal  Cases  of  Malaria.  By  LEWELLYS 
P.  BABKEB,  M.  B.  280  pages.  Price,  in  paper,  $2.75. 

The  Pathology  of  Toxalbumin  Intoxications.  By  SIMON  FLEXNEB,  M.  D. 
150  pages  with  4  lithographs.  Price,  in  paper,  $2.00. 

Studies  in  Typhoid  Fever,  I,  n,  HI.  By  WILLIAM  OSLEB,  M.  D.,  and  others. 
Extracted  from  Vols.  IV,  V  and  VIII  of  the  Reports.  757  pages. 
Price,  in  cloth,  $5.00. 

Pneumothorax.  A  Historical,  Clinical,  and  Experimental  Study.  By 
CHABLES  P.  EMERSON,  M.  D.  Price,  in  paper,  $4.00. 

NEW  SERIES. 

I.  Free  Thrombi  and  Ball-Thrombi  in  the  Heart.    By  J.  H.  HEWITT,  M.  D. 
82  pages  and  20  illustrations.    Price,  in  paper,  $1.00. 

II.  Benzol  as  a  Leucotoxin.  By  LAURENCE  SELLING,  M.  D.  60  pages  and 
3  plates,  1  in  colors.  Price,  in  paper,  $1.00. 

III.  Primary  Carcinoma  of  the  liver.  By  M.  C.  WINTEBNTTZ,  M.  D.  42 
pages.  Price,  in  paper,  75  cents. 

IV.  The  Statistical  Experience  Data  of  The  Johns  Hopkins  Hospital,  Balti- 
more, Md.,  1892-1911.  By  FREDERICK  L.  HOFFMAN,  L»L.  D.,  F.  S.  S.  161 
pages.  Price,  in  paper,  $2.00. 

V.  The  Origin  and  Development  of  the  Lymphatic  System.  By  FLORENCE  R. 
SABIN.  94  pages.  Price,  in  paper,  $2.00. 

VI.  The  Nuclei  Tuberis  Laterales  and  the  So-called  Ganglion  Opticum  Basale. 
By  EDWARD  F.  MALONE.   70  pages  and  15  plates.    Price,  in  paper,  $1.00. 

VII.  Venous  Thrombosis  During  Myocardial  Insufficiency.      By  F.  J.  SLADEN, 
M.  D.,  and  M.  C.  WINTERNITZ,  M.  D.   40  pages  and  2  figures,  and  1  plate 
in  colors.    Price,  in  paper,  75  cents. 

VIII. Leukaemia  of  the  Fowl:    Spontaneous  and  Experimental.     By  HARRY  C. 
~KR,  M.  D.    34  pages  and  4  plates,  2  in  colors.    Price,  in  paper, 
$2.00. 


Gaylamount 

Pamphlet 

Binder 

Gay  lord  Bros.,  Inc. 

Stockton,  Calif. 
T.M.  Reg-  U.S.  Pat.  Off. 


THIS  BOOK  IS  DUE  ON  THE  LAST  DATE 
STAMPED  BELOW 


AN  INITIAL  FINE  OF  25  CENTS 

WILL  BE  ASSESSED  FOR  FAILURE  TO  RETURN 
THIS  BOOK  ON  THE  DATE  DUE.  THE  PENALTY 
WILL  INCREASE  TO  SO  CENTS  ON  THE  FOURTH 
DAY  AND  TO  $1.OO  ON  THE  SEVENTH  DAY 
OVERDUE. 


Ml    8  1950 


OCT  i  s  m 


IS 


41528,3 


UNIVERSITY  OF  CALIFORNIA  LIBRARY 


LD  2l-95m-7,'37 


